Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02; http://priors.hci.utah.edu/PRIORS/), AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/), AND minor allele frequency 0.00119 (East Asian), derived from gnomAD v2.1.1 non-cancer (2019-05-13).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3448C>T (p.Pro1150Ser)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Jun 2019 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.3448C>T (p.Pro1150Ser)
Variation ID: 54887 Accession: VCV000054887.33
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43092083 (GRCh38) [ NCBI UCSC ] 17: 41244100 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Oct 8, 2024 Jun 18, 2019 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3448C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Pro1150Ser missense NM_001407571.1:c.3235C>T NP_001394500.1:p.Pro1079Ser missense NM_001407581.1:c.3448C>T NP_001394510.1:p.Pro1150Ser missense NM_001407582.1:c.3448C>T NP_001394511.1:p.Pro1150Ser missense NM_001407583.1:c.3448C>T NP_001394512.1:p.Pro1150Ser missense NM_001407585.1:c.3448C>T NP_001394514.1:p.Pro1150Ser missense NM_001407587.1:c.3445C>T NP_001394516.1:p.Pro1149Ser missense NM_001407590.1:c.3445C>T NP_001394519.1:p.Pro1149Ser missense NM_001407591.1:c.3445C>T NP_001394520.1:p.Pro1149Ser missense NM_001407593.1:c.3448C>T NP_001394522.1:p.Pro1150Ser missense NM_001407594.1:c.3448C>T NP_001394523.1:p.Pro1150Ser missense NM_001407596.1:c.3448C>T NP_001394525.1:p.Pro1150Ser missense NM_001407597.1:c.3448C>T NP_001394526.1:p.Pro1150Ser missense NM_001407598.1:c.3448C>T NP_001394527.1:p.Pro1150Ser missense NM_001407602.1:c.3448C>T NP_001394531.1:p.Pro1150Ser missense NM_001407603.1:c.3448C>T NP_001394532.1:p.Pro1150Ser missense NM_001407605.1:c.3448C>T NP_001394534.1:p.Pro1150Ser missense NM_001407610.1:c.3445C>T NP_001394539.1:p.Pro1149Ser missense NM_001407611.1:c.3445C>T NP_001394540.1:p.Pro1149Ser missense NM_001407612.1:c.3445C>T NP_001394541.1:p.Pro1149Ser missense NM_001407613.1:c.3445C>T NP_001394542.1:p.Pro1149Ser missense NM_001407614.1:c.3445C>T NP_001394543.1:p.Pro1149Ser missense NM_001407615.1:c.3445C>T NP_001394544.1:p.Pro1149Ser missense NM_001407616.1:c.3448C>T NP_001394545.1:p.Pro1150Ser missense NM_001407617.1:c.3448C>T NP_001394546.1:p.Pro1150Ser missense NM_001407618.1:c.3448C>T NP_001394547.1:p.Pro1150Ser missense NM_001407619.1:c.3448C>T NP_001394548.1:p.Pro1150Ser missense NM_001407620.1:c.3448C>T NP_001394549.1:p.Pro1150Ser missense NM_001407621.1:c.3448C>T NP_001394550.1:p.Pro1150Ser missense NM_001407622.1:c.3448C>T NP_001394551.1:p.Pro1150Ser missense NM_001407623.1:c.3448C>T NP_001394552.1:p.Pro1150Ser missense NM_001407624.1:c.3448C>T NP_001394553.1:p.Pro1150Ser missense NM_001407625.1:c.3448C>T NP_001394554.1:p.Pro1150Ser missense NM_001407626.1:c.3448C>T NP_001394555.1:p.Pro1150Ser missense NM_001407627.1:c.3445C>T NP_001394556.1:p.Pro1149Ser missense NM_001407628.1:c.3445C>T NP_001394557.1:p.Pro1149Ser missense NM_001407629.1:c.3445C>T NP_001394558.1:p.Pro1149Ser missense NM_001407630.1:c.3445C>T NP_001394559.1:p.Pro1149Ser missense NM_001407631.1:c.3445C>T NP_001394560.1:p.Pro1149Ser missense NM_001407632.1:c.3445C>T NP_001394561.1:p.Pro1149Ser missense NM_001407633.1:c.3445C>T NP_001394562.1:p.Pro1149Ser missense NM_001407634.1:c.3445C>T NP_001394563.1:p.Pro1149Ser missense NM_001407635.1:c.3445C>T NP_001394564.1:p.Pro1149Ser missense NM_001407636.1:c.3445C>T NP_001394565.1:p.Pro1149Ser missense NM_001407637.1:c.3445C>T NP_001394566.1:p.Pro1149Ser missense NM_001407638.1:c.3445C>T NP_001394567.1:p.Pro1149Ser missense NM_001407639.1:c.3448C>T NP_001394568.1:p.Pro1150Ser missense NM_001407640.1:c.3448C>T NP_001394569.1:p.Pro1150Ser missense NM_001407641.1:c.3448C>T NP_001394570.1:p.Pro1150Ser missense NM_001407642.1:c.3448C>T NP_001394571.1:p.Pro1150Ser missense NM_001407644.1:c.3445C>T NP_001394573.1:p.Pro1149Ser missense NM_001407645.1:c.3445C>T NP_001394574.1:p.Pro1149Ser missense NM_001407646.1:c.3439C>T NP_001394575.1:p.Pro1147Ser missense NM_001407647.1:c.3439C>T NP_001394576.1:p.Pro1147Ser missense NM_001407648.1:c.3325C>T NP_001394577.1:p.Pro1109Ser missense NM_001407649.1:c.3322C>T NP_001394578.1:p.Pro1108Ser missense NM_001407652.1:c.3448C>T NP_001394581.1:p.Pro1150Ser missense NM_001407653.1:c.3370C>T NP_001394582.1:p.Pro1124Ser missense NM_001407654.1:c.3370C>T NP_001394583.1:p.Pro1124Ser missense NM_001407655.1:c.3370C>T NP_001394584.1:p.Pro1124Ser missense NM_001407656.1:c.3370C>T NP_001394585.1:p.Pro1124Ser missense NM_001407657.1:c.3370C>T NP_001394586.1:p.Pro1124Ser missense NM_001407658.1:c.3370C>T NP_001394587.1:p.Pro1124Ser missense NM_001407659.1:c.3367C>T NP_001394588.1:p.Pro1123Ser missense NM_001407660.1:c.3367C>T NP_001394589.1:p.Pro1123Ser missense NM_001407661.1:c.3367C>T NP_001394590.1:p.Pro1123Ser missense NM_001407662.1:c.3367C>T NP_001394591.1:p.Pro1123Ser missense NM_001407663.1:c.3370C>T NP_001394592.1:p.Pro1124Ser missense NM_001407664.1:c.3325C>T NP_001394593.1:p.Pro1109Ser missense NM_001407665.1:c.3325C>T NP_001394594.1:p.Pro1109Ser missense NM_001407666.1:c.3325C>T NP_001394595.1:p.Pro1109Ser missense NM_001407667.1:c.3325C>T NP_001394596.1:p.Pro1109Ser missense NM_001407668.1:c.3325C>T NP_001394597.1:p.Pro1109Ser missense NM_001407669.1:c.3325C>T NP_001394598.1:p.Pro1109Ser missense NM_001407670.1:c.3322C>T NP_001394599.1:p.Pro1108Ser missense NM_001407671.1:c.3322C>T NP_001394600.1:p.Pro1108Ser missense NM_001407672.1:c.3322C>T NP_001394601.1:p.Pro1108Ser missense NM_001407673.1:c.3322C>T NP_001394602.1:p.Pro1108Ser missense NM_001407674.1:c.3325C>T NP_001394603.1:p.Pro1109Ser missense NM_001407675.1:c.3325C>T NP_001394604.1:p.Pro1109Ser missense NM_001407676.1:c.3325C>T NP_001394605.1:p.Pro1109Ser missense NM_001407677.1:c.3325C>T NP_001394606.1:p.Pro1109Ser missense NM_001407678.1:c.3325C>T NP_001394607.1:p.Pro1109Ser missense NM_001407679.1:c.3325C>T NP_001394608.1:p.Pro1109Ser missense NM_001407680.1:c.3325C>T NP_001394609.1:p.Pro1109Ser missense NM_001407681.1:c.3325C>T NP_001394610.1:p.Pro1109Ser missense NM_001407682.1:c.3325C>T NP_001394611.1:p.Pro1109Ser missense NM_001407683.1:c.3325C>T NP_001394612.1:p.Pro1109Ser missense NM_001407684.1:c.3448C>T NP_001394613.1:p.Pro1150Ser missense NM_001407685.1:c.3322C>T NP_001394614.1:p.Pro1108Ser missense NM_001407686.1:c.3322C>T NP_001394615.1:p.Pro1108Ser missense NM_001407687.1:c.3322C>T NP_001394616.1:p.Pro1108Ser missense NM_001407688.1:c.3322C>T NP_001394617.1:p.Pro1108Ser missense NM_001407689.1:c.3322C>T NP_001394618.1:p.Pro1108Ser missense NM_001407690.1:c.3322C>T NP_001394619.1:p.Pro1108Ser missense NM_001407691.1:c.3322C>T NP_001394620.1:p.Pro1108Ser missense NM_001407692.1:c.3307C>T NP_001394621.1:p.Pro1103Ser missense NM_001407694.1:c.3307C>T NP_001394623.1:p.Pro1103Ser missense NM_001407695.1:c.3307C>T NP_001394624.1:p.Pro1103Ser missense NM_001407696.1:c.3307C>T NP_001394625.1:p.Pro1103Ser missense NM_001407697.1:c.3307C>T NP_001394626.1:p.Pro1103Ser missense NM_001407698.1:c.3307C>T NP_001394627.1:p.Pro1103Ser missense NM_001407724.1:c.3307C>T NP_001394653.1:p.Pro1103Ser missense NM_001407725.1:c.3307C>T NP_001394654.1:p.Pro1103Ser missense NM_001407726.1:c.3307C>T NP_001394655.1:p.Pro1103Ser missense NM_001407727.1:c.3307C>T NP_001394656.1:p.Pro1103Ser missense NM_001407728.1:c.3307C>T NP_001394657.1:p.Pro1103Ser missense NM_001407729.1:c.3307C>T NP_001394658.1:p.Pro1103Ser missense NM_001407730.1:c.3307C>T NP_001394659.1:p.Pro1103Ser missense NM_001407731.1:c.3307C>T NP_001394660.1:p.Pro1103Ser missense NM_001407732.1:c.3307C>T NP_001394661.1:p.Pro1103Ser missense NM_001407733.1:c.3307C>T NP_001394662.1:p.Pro1103Ser missense NM_001407734.1:c.3307C>T NP_001394663.1:p.Pro1103Ser missense NM_001407735.1:c.3307C>T NP_001394664.1:p.Pro1103Ser missense NM_001407736.1:c.3307C>T NP_001394665.1:p.Pro1103Ser missense NM_001407737.1:c.3307C>T NP_001394666.1:p.Pro1103Ser missense NM_001407738.1:c.3307C>T NP_001394667.1:p.Pro1103Ser missense NM_001407739.1:c.3307C>T NP_001394668.1:p.Pro1103Ser missense NM_001407740.1:c.3304C>T NP_001394669.1:p.Pro1102Ser missense NM_001407741.1:c.3304C>T NP_001394670.1:p.Pro1102Ser missense NM_001407742.1:c.3304C>T NP_001394671.1:p.Pro1102Ser missense NM_001407743.1:c.3304C>T NP_001394672.1:p.Pro1102Ser missense NM_001407744.1:c.3304C>T NP_001394673.1:p.Pro1102Ser missense NM_001407745.1:c.3304C>T NP_001394674.1:p.Pro1102Ser missense NM_001407746.1:c.3304C>T NP_001394675.1:p.Pro1102Ser missense NM_001407747.1:c.3304C>T NP_001394676.1:p.Pro1102Ser missense NM_001407748.1:c.3304C>T NP_001394677.1:p.Pro1102Ser missense NM_001407749.1:c.3304C>T NP_001394678.1:p.Pro1102Ser missense NM_001407750.1:c.3307C>T NP_001394679.1:p.Pro1103Ser missense NM_001407751.1:c.3307C>T NP_001394680.1:p.Pro1103Ser missense NM_001407752.1:c.3307C>T NP_001394681.1:p.Pro1103Ser missense NM_001407838.1:c.3304C>T NP_001394767.1:p.Pro1102Ser missense NM_001407839.1:c.3304C>T NP_001394768.1:p.Pro1102Ser missense NM_001407841.1:c.3304C>T NP_001394770.1:p.Pro1102Ser missense NM_001407842.1:c.3304C>T NP_001394771.1:p.Pro1102Ser missense NM_001407843.1:c.3304C>T NP_001394772.1:p.Pro1102Ser missense NM_001407844.1:c.3304C>T NP_001394773.1:p.Pro1102Ser missense NM_001407845.1:c.3304C>T NP_001394774.1:p.Pro1102Ser missense NM_001407846.1:c.3304C>T NP_001394775.1:p.Pro1102Ser missense NM_001407847.1:c.3304C>T NP_001394776.1:p.Pro1102Ser missense NM_001407848.1:c.3304C>T NP_001394777.1:p.Pro1102Ser missense NM_001407849.1:c.3304C>T NP_001394778.1:p.Pro1102Ser missense NM_001407850.1:c.3307C>T NP_001394779.1:p.Pro1103Ser missense NM_001407851.1:c.3307C>T NP_001394780.1:p.Pro1103Ser missense NM_001407852.1:c.3307C>T NP_001394781.1:p.Pro1103Ser missense NM_001407853.1:c.3235C>T NP_001394782.1:p.Pro1079Ser missense NM_001407854.1:c.3448C>T NP_001394783.1:p.Pro1150Ser missense NM_001407858.1:c.3448C>T NP_001394787.1:p.Pro1150Ser missense NM_001407859.1:c.3448C>T NP_001394788.1:p.Pro1150Ser missense NM_001407860.1:c.3445C>T NP_001394789.1:p.Pro1149Ser missense NM_001407861.1:c.3445C>T NP_001394790.1:p.Pro1149Ser missense NM_001407862.1:c.3247C>T NP_001394791.1:p.Pro1083Ser missense NM_001407863.1:c.3325C>T NP_001394792.1:p.Pro1109Ser missense NM_001407874.1:c.3244C>T NP_001394803.1:p.Pro1082Ser missense NM_001407875.1:c.3244C>T NP_001394804.1:p.Pro1082Ser missense NM_001407879.1:c.3238C>T NP_001394808.1:p.Pro1080Ser missense NM_001407881.1:c.3238C>T NP_001394810.1:p.Pro1080Ser missense NM_001407882.1:c.3238C>T NP_001394811.1:p.Pro1080Ser missense NM_001407884.1:c.3238C>T NP_001394813.1:p.Pro1080Ser missense NM_001407885.1:c.3238C>T NP_001394814.1:p.Pro1080Ser missense NM_001407886.1:c.3238C>T NP_001394815.1:p.Pro1080Ser missense NM_001407887.1:c.3238C>T NP_001394816.1:p.Pro1080Ser missense NM_001407889.1:c.3238C>T NP_001394818.1:p.Pro1080Ser missense NM_001407894.1:c.3235C>T NP_001394823.1:p.Pro1079Ser missense NM_001407895.1:c.3235C>T NP_001394824.1:p.Pro1079Ser missense NM_001407896.1:c.3235C>T NP_001394825.1:p.Pro1079Ser missense NM_001407897.1:c.3235C>T NP_001394826.1:p.Pro1079Ser missense NM_001407898.1:c.3235C>T NP_001394827.1:p.Pro1079Ser missense NM_001407899.1:c.3235C>T NP_001394828.1:p.Pro1079Ser missense NM_001407900.1:c.3238C>T NP_001394829.1:p.Pro1080Ser missense NM_001407902.1:c.3238C>T NP_001394831.1:p.Pro1080Ser missense NM_001407904.1:c.3238C>T NP_001394833.1:p.Pro1080Ser missense NM_001407906.1:c.3238C>T NP_001394835.1:p.Pro1080Ser missense NM_001407907.1:c.3238C>T NP_001394836.1:p.Pro1080Ser missense NM_001407908.1:c.3238C>T NP_001394837.1:p.Pro1080Ser missense NM_001407909.1:c.3238C>T NP_001394838.1:p.Pro1080Ser missense NM_001407910.1:c.3238C>T NP_001394839.1:p.Pro1080Ser missense NM_001407915.1:c.3235C>T NP_001394844.1:p.Pro1079Ser missense NM_001407916.1:c.3235C>T NP_001394845.1:p.Pro1079Ser missense NM_001407917.1:c.3235C>T NP_001394846.1:p.Pro1079Ser missense NM_001407918.1:c.3235C>T NP_001394847.1:p.Pro1079Ser missense NM_001407919.1:c.3325C>T NP_001394848.1:p.Pro1109Ser missense NM_001407920.1:c.3184C>T NP_001394849.1:p.Pro1062Ser missense NM_001407921.1:c.3184C>T NP_001394850.1:p.Pro1062Ser missense NM_001407922.1:c.3184C>T NP_001394851.1:p.Pro1062Ser missense NM_001407923.1:c.3184C>T NP_001394852.1:p.Pro1062Ser missense NM_001407924.1:c.3184C>T NP_001394853.1:p.Pro1062Ser missense NM_001407925.1:c.3184C>T NP_001394854.1:p.Pro1062Ser missense NM_001407926.1:c.3184C>T NP_001394855.1:p.Pro1062Ser missense NM_001407927.1:c.3184C>T NP_001394856.1:p.Pro1062Ser missense NM_001407928.1:c.3184C>T NP_001394857.1:p.Pro1062Ser missense NM_001407929.1:c.3184C>T NP_001394858.1:p.Pro1062Ser missense NM_001407930.1:c.3181C>T NP_001394859.1:p.Pro1061Ser missense NM_001407931.1:c.3181C>T NP_001394860.1:p.Pro1061Ser missense NM_001407932.1:c.3181C>T NP_001394861.1:p.Pro1061Ser missense NM_001407933.1:c.3184C>T NP_001394862.1:p.Pro1062Ser missense NM_001407934.1:c.3181C>T NP_001394863.1:p.Pro1061Ser missense NM_001407935.1:c.3184C>T NP_001394864.1:p.Pro1062Ser missense NM_001407936.1:c.3181C>T NP_001394865.1:p.Pro1061Ser missense NM_001407937.1:c.3325C>T NP_001394866.1:p.Pro1109Ser missense NM_001407938.1:c.3325C>T NP_001394867.1:p.Pro1109Ser missense NM_001407939.1:c.3325C>T NP_001394868.1:p.Pro1109Ser missense NM_001407940.1:c.3322C>T NP_001394869.1:p.Pro1108Ser missense NM_001407941.1:c.3322C>T NP_001394870.1:p.Pro1108Ser missense NM_001407942.1:c.3307C>T NP_001394871.1:p.Pro1103Ser missense NM_001407943.1:c.3304C>T NP_001394872.1:p.Pro1102Ser missense NM_001407944.1:c.3307C>T NP_001394873.1:p.Pro1103Ser missense NM_001407945.1:c.3307C>T NP_001394874.1:p.Pro1103Ser missense NM_001407946.1:c.3115C>T NP_001394875.1:p.Pro1039Ser missense NM_001407947.1:c.3115C>T NP_001394876.1:p.Pro1039Ser missense NM_001407948.1:c.3115C>T NP_001394877.1:p.Pro1039Ser missense NM_001407949.1:c.3115C>T NP_001394878.1:p.Pro1039Ser missense NM_001407950.1:c.3115C>T NP_001394879.1:p.Pro1039Ser missense NM_001407951.1:c.3115C>T NP_001394880.1:p.Pro1039Ser missense NM_001407952.1:c.3115C>T NP_001394881.1:p.Pro1039Ser missense NM_001407953.1:c.3115C>T NP_001394882.1:p.Pro1039Ser missense NM_001407954.1:c.3112C>T NP_001394883.1:p.Pro1038Ser missense NM_001407955.1:c.3112C>T NP_001394884.1:p.Pro1038Ser missense NM_001407956.1:c.3112C>T NP_001394885.1:p.Pro1038Ser missense NM_001407957.1:c.3115C>T NP_001394886.1:p.Pro1039Ser missense NM_001407958.1:c.3112C>T NP_001394887.1:p.Pro1038Ser missense NM_001407959.1:c.3067C>T NP_001394888.1:p.Pro1023Ser missense NM_001407960.1:c.3067C>T NP_001394889.1:p.Pro1023Ser missense NM_001407962.1:c.3064C>T NP_001394891.1:p.Pro1022Ser missense NM_001407963.1:c.3067C>T NP_001394892.1:p.Pro1023Ser missense NM_001407964.1:c.3304C>T NP_001394893.1:p.Pro1102Ser missense NM_001407965.1:c.2944C>T NP_001394894.1:p.Pro982Ser missense NM_001407966.1:c.2560C>T NP_001394895.1:p.Pro854Ser missense NM_001407967.1:c.2560C>T NP_001394896.1:p.Pro854Ser missense NM_001407968.1:c.844C>T NP_001394897.1:p.Pro282Ser missense NM_001407969.1:c.844C>T NP_001394898.1:p.Pro282Ser missense NM_001407970.1:c.788-1051C>T intron variant NM_001407971.1:c.788-1051C>T intron variant NM_001407972.1:c.785-1051C>T intron variant NM_001407973.1:c.788-1051C>T intron variant NM_001407974.1:c.788-1051C>T intron variant NM_001407975.1:c.788-1051C>T intron variant NM_001407976.1:c.788-1051C>T intron variant NM_001407977.1:c.788-1051C>T intron variant NM_001407978.1:c.788-1051C>T intron variant NM_001407979.1:c.788-1051C>T intron variant NM_001407980.1:c.788-1051C>T intron variant NM_001407981.1:c.788-1051C>T intron variant NM_001407982.1:c.788-1051C>T intron variant NM_001407983.1:c.788-1051C>T intron variant NM_001407984.1:c.785-1051C>T intron variant NM_001407985.1:c.785-1051C>T intron variant NM_001407986.1:c.785-1051C>T intron variant NM_001407990.1:c.788-1051C>T intron variant NM_001407991.1:c.785-1051C>T intron variant NM_001407992.1:c.785-1051C>T intron variant NM_001407993.1:c.788-1051C>T intron variant NM_001408392.1:c.785-1051C>T intron variant NM_001408396.1:c.785-1051C>T intron variant NM_001408397.1:c.785-1051C>T intron variant NM_001408398.1:c.785-1051C>T intron variant NM_001408399.1:c.785-1051C>T intron variant NM_001408400.1:c.785-1051C>T intron variant NM_001408401.1:c.785-1051C>T intron variant NM_001408402.1:c.785-1051C>T intron variant NM_001408403.1:c.788-1051C>T intron variant NM_001408404.1:c.788-1051C>T intron variant NM_001408406.1:c.791-1060C>T intron variant NM_001408407.1:c.785-1051C>T intron variant NM_001408408.1:c.779-1051C>T intron variant NM_001408409.1:c.710-1051C>T intron variant NM_001408410.1:c.647-1051C>T intron variant NM_001408411.1:c.710-1051C>T intron variant NM_001408412.1:c.710-1051C>T intron variant NM_001408413.1:c.707-1051C>T intron variant NM_001408414.1:c.710-1051C>T intron variant NM_001408415.1:c.710-1051C>T intron variant NM_001408416.1:c.707-1051C>T intron variant NM_001408418.1:c.671-1051C>T intron variant NM_001408419.1:c.671-1051C>T intron variant NM_001408420.1:c.671-1051C>T intron variant NM_001408421.1:c.668-1051C>T intron variant NM_001408422.1:c.671-1051C>T intron variant NM_001408423.1:c.671-1051C>T intron variant NM_001408424.1:c.668-1051C>T intron variant NM_001408425.1:c.665-1051C>T intron variant NM_001408426.1:c.665-1051C>T intron variant NM_001408427.1:c.665-1051C>T intron variant NM_001408428.1:c.665-1051C>T intron variant NM_001408429.1:c.665-1051C>T intron variant NM_001408430.1:c.665-1051C>T intron variant NM_001408431.1:c.668-1051C>T intron variant NM_001408432.1:c.662-1051C>T intron variant NM_001408433.1:c.662-1051C>T intron variant NM_001408434.1:c.662-1051C>T intron variant NM_001408435.1:c.662-1051C>T intron variant NM_001408436.1:c.665-1051C>T intron variant NM_001408437.1:c.665-1051C>T intron variant NM_001408438.1:c.665-1051C>T intron variant NM_001408439.1:c.665-1051C>T intron variant NM_001408440.1:c.665-1051C>T intron variant NM_001408441.1:c.665-1051C>T intron variant NM_001408442.1:c.665-1051C>T intron variant NM_001408443.1:c.665-1051C>T intron variant NM_001408444.1:c.665-1051C>T intron variant NM_001408445.1:c.662-1051C>T intron variant NM_001408446.1:c.662-1051C>T intron variant NM_001408447.1:c.662-1051C>T intron variant NM_001408448.1:c.662-1051C>T intron variant NM_001408450.1:c.662-1051C>T intron variant NM_001408451.1:c.653-1051C>T intron variant NM_001408452.1:c.647-1051C>T intron variant NM_001408453.1:c.647-1051C>T intron variant NM_001408454.1:c.647-1051C>T intron variant NM_001408455.1:c.647-1051C>T intron variant NM_001408456.1:c.647-1051C>T intron variant NM_001408457.1:c.647-1051C>T intron variant NM_001408458.1:c.647-1051C>T intron variant NM_001408459.1:c.647-1051C>T intron variant NM_001408460.1:c.647-1051C>T intron variant NM_001408461.1:c.647-1051C>T intron variant NM_001408462.1:c.644-1051C>T intron variant NM_001408463.1:c.644-1051C>T intron variant NM_001408464.1:c.644-1051C>T intron variant NM_001408465.1:c.644-1051C>T intron variant NM_001408466.1:c.647-1051C>T intron variant NM_001408467.1:c.647-1051C>T intron variant NM_001408468.1:c.644-1051C>T intron variant NM_001408469.1:c.647-1051C>T intron variant NM_001408470.1:c.644-1051C>T intron variant NM_001408472.1:c.788-1051C>T intron variant NM_001408473.1:c.785-1051C>T intron variant NM_001408474.1:c.587-1051C>T intron variant NM_001408475.1:c.584-1051C>T intron variant NM_001408476.1:c.587-1051C>T intron variant NM_001408478.1:c.578-1051C>T intron variant NM_001408479.1:c.578-1051C>T intron variant NM_001408480.1:c.578-1051C>T intron variant NM_001408481.1:c.578-1051C>T intron variant NM_001408482.1:c.578-1051C>T intron variant NM_001408483.1:c.578-1051C>T intron variant NM_001408484.1:c.578-1051C>T intron variant NM_001408485.1:c.578-1051C>T intron variant NM_001408489.1:c.578-1051C>T intron variant NM_001408490.1:c.575-1051C>T intron variant NM_001408491.1:c.575-1051C>T intron variant NM_001408492.1:c.578-1051C>T intron variant NM_001408493.1:c.575-1051C>T intron variant NM_001408494.1:c.548-1051C>T intron variant NM_001408495.1:c.545-1051C>T intron variant NM_001408496.1:c.524-1051C>T intron variant NM_001408497.1:c.524-1051C>T intron variant NM_001408498.1:c.524-1051C>T intron variant NM_001408499.1:c.524-1051C>T intron variant NM_001408500.1:c.524-1051C>T intron variant NM_001408501.1:c.524-1051C>T intron variant NM_001408502.1:c.455-1051C>T intron variant NM_001408503.1:c.521-1051C>T intron variant NM_001408504.1:c.521-1051C>T intron variant NM_001408505.1:c.521-1051C>T intron variant NM_001408506.1:c.461-1051C>T intron variant NM_001408507.1:c.461-1051C>T intron variant NM_001408508.1:c.452-1051C>T intron variant NM_001408509.1:c.452-1051C>T intron variant NM_001408510.1:c.407-1051C>T intron variant NM_001408511.1:c.404-1051C>T intron variant NM_001408512.1:c.284-1051C>T intron variant NM_001408513.1:c.578-1051C>T intron variant NM_001408514.1:c.578-1051C>T intron variant NM_007297.4:c.3307C>T NP_009228.2:p.Pro1103Ser missense NM_007298.4:c.788-1051C>T intron variant NM_007299.4:c.788-1051C>T intron variant NM_007300.4:c.3448C>T NP_009231.2:p.Pro1150Ser missense NR_027676.1:n.3584C>T NC_000017.11:g.43092083G>A NC_000017.10:g.41244100G>A NG_005905.2:g.125901C>T NG_087068.1:g.1065G>A LRG_292:g.125901C>T LRG_292t1:c.3448C>T LRG_292p1:p.Pro1150Ser P38398:p.Pro1150Ser U14680.1:n.3567C>T - Protein change
- P1150S, P1103S, P1022S, P1039S, P282S, P1023S, P1038S, P1062S, P1082S, P1109S, P1147S, P1061S, P1102S, P1108S, P1124S, P1079S, P1080S, P1083S, P1123S, P1149S, P854S, P982S
- Other names
- -
- Canonical SPDI
- NC_000017.11:43092082:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00080 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00010
1000 Genomes Project 0.00080
1000 Genomes Project 30x 0.00109
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00005
Exome Aggregation Consortium (ExAC) 0.00009
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13044 | 14850 | |
| LOC126862571 | - | - | - | GRCh38 | - | 1651 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 22, 2021 | RCV000131184.17 | |
| Benign (5) |
reviewed by expert panel
|
Jun 18, 2019 | RCV000112099.18 | |
| Benign (2) |
criteria provided, single submitter
|
Jun 23, 2022 | RCV000483961.17 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
May 11, 2023 | RCV000587116.18 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 30, 2024 | RCV001080313.14 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jan 1, 2022 | RCV003153339.9 | |
| Uncertain significance (1) |
no assertion criteria provided
|
- | RCV002250536.9 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 10, 2017 | RCV000240742.9 | |
|
BRCA1-related disorder
|
Uncertain significance (1) |
no assertion criteria provided
|
Jun 3, 2024 | RCV004758626.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Jun 18, 2019)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV001161572.2
First in ClinVar: Feb 16, 2020 Last updated: Jan 07, 2023 |
Comment:
Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02; http://priors.hci.utah.edu/PRIORS/), AND low bioinformatic likelihood to alter … (more)
Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02; http://priors.hci.utah.edu/PRIORS/), AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/), AND minor allele frequency 0.00119 (East Asian), derived from gnomAD v2.1.1 non-cancer (2019-05-13). (less)
|
|
|
Uncertain significance
(Nov 01, 2015)
|
criteria provided, single submitter
Method: research
|
Breast neoplasm
Affected status: yes
Allele origin:
germline
|
Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University
Additional submitter:
Asia and Emerging Markets iMed, AstraZeneca
Accession: SCV000265876.1
First in ClinVar: Sep 14, 2016 Last updated: Sep 14, 2016 |
Number of individuals with the variant: 1
Geographic origin: China
|
|
|
Uncertain significance
(Oct 04, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000568411.5
First in ClinVar: Apr 29, 2017 Last updated: Mar 17, 2018 |
Comment:
This variant is denoted BRCA1 c.3448C>T at the cDNA level, p.Pro1150Ser (P1150S) at the protein level, and results in the change of a Proline to … (more)
This variant is denoted BRCA1 c.3448C>T at the cDNA level, p.Pro1150Ser (P1150S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). Using alternate nomenclature, this variant has been previously published as BRCA1 3567C>T. This variant was observed in individuals with breast cancer, but was also seen in controls (Katagiri 1996, Tang 1999, Belogianni 2004, Jang 2012, Yoon 2016, Zhong 2016, Li 2017, Ryu 2017). A homologous-directed repair assay demonstrated that this variant results in homologous recombination activity similar to the wildtype protein (Lu 2015). BRCA1 Pro1150Ser was observed at an allele frequency of 0.095% (18/18866) in individuals of East Asian ancestry in large population cohorts (Lek 2016). Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro1150Ser occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Pro1150Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
|
|
|
Likely benign
(Dec 30, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000902976.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
|
Likely benign
(Oct 22, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002538210.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
|
Likely pathogenic
(Jan 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Ovarian cancer
Affected status: yes
Allele origin:
germline
|
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University
Accession: SCV003843686.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
|
|
|
Benign
(May 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001133552.5
First in ClinVar: Jan 05, 2020 Last updated: Jan 06, 2024 |
|
|
|
Benign
(Jan 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076213.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
|
|
|
Uncertain significance
(Jun 10, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Neoplasm of the breast
Affected status: yes
Allele origin:
germline
|
3DMed Clinical Laboratory Inc
Accession: SCV000803955.1
First in ClinVar: Sep 14, 2016 Last updated: Sep 14, 2016 |
|
|
|
Benign
(Jun 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699033.2
First in ClinVar: Mar 17, 2018 Last updated: Aug 08, 2022 |
Comment:
Variant summary: BRCA1 c.3448C>T (p.Pro1150Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Variant summary: BRCA1 c.3448C>T (p.Pro1150Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251790 control chromosomes, predominantly at a frequency of 0.0013 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.3448C>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer, without strong evidence for pathogenicity (example, Haffty_2009, Haiman_2013, Liang_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least one co-occurrence with another pathogenic variant(s) have been reported in the UMD database (BRCA1 c.3181delA, p.Ile1061X), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function (example, Lu_2015). The most pronounced variant effect results in approximately 89% of normal homology directed repair (HDR) activity suggestive of a non-significant impact on protein function. Multiple clinical diagnostic laboratories and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 with a predominant consensus as benign/likely benign to include the expert panel. Based on the evidence outlined above, the variant was classified as benign. (less)
|
|
|
Benign
(Aug 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV001140553.2
First in ClinVar: Jan 09, 2020 Last updated: Aug 25, 2023 |
|
|
|
Likely Benign
(Dec 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004817800.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 4
|
|
|
Likely benign
(Jun 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186131.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Uncertain significance
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144767.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 5
|
|
|
Uncertain significance
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
not specified
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587311.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: literature only
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
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Center for Precision Medicine, Meizhou People's Hospital
Accession: SCV002520877.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
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Uncertain significance
(Jun 03, 2024)
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no assertion criteria provided
Method: clinical testing
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BRCA1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005362286.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The BRCA1 c.3448C>T variant is predicted to result in the amino acid substitution p.Pro1150Ser. This variant has been reported in patients with breast or ovarian … (more)
The BRCA1 c.3448C>T variant is predicted to result in the amino acid substitution p.Pro1150Ser. This variant has been reported in patients with breast or ovarian cancer, although pathogenicity was not clearly established (Emi et al. 1998. PubMed ID: 9510469; Yang et al. 2017. PubMed ID: 28664506; Eoh et al. 2017. PubMed ID: 29020732; Li et al. 2019. PubMed ID: 29752822; So et al. 2019. PubMed ID: 30725392). It has been observed in both cases and controls in a study of breast cancer patients (Momozawa et al. 2018. PubMed ID: 30287823) and has been reported as likely benign due to co-occurrence with a pathogenic variant (Lee et al. 2018. PubMed ID: 30415210). This variant has been reported at a frequency of ~0.1% in individuals of East Asian origin in the gnomAD database and is classified as benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/54887/). An internal summary of amino acid substitution prediction programs predicts the p.Pro1150Ser change to be “damaging” (Liu et al. 2016. PMID: 26555599). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549557.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The BRCA1 p.Pro1150Ser variant was identified in 13 of 4830 proband chromosomes (frequency: 0.003) from Chinese and Korean individuals or families with breast cancer, and … (more)
The BRCA1 p.Pro1150Ser variant was identified in 13 of 4830 proband chromosomes (frequency: 0.003) from Chinese and Korean individuals or families with breast cancer, and in 3 of 1892 control chromosomes (frequency: 0.002) from healthy individuals (Tang 1999, Li 2017 , Jang 2012, Suter 2004, Yang 2017, Yoon 2016). The variant was also identified in dbSNP (ID: rs80357272) as “With other allele”, in ClinVar (classified with conflicting interpretations of pathogenicity; submitters: uncertain significance by Ambry Genetics, CHEO Genetics Diagnostic Laboratory, Laboratory of Molecular Diagnosis of Cancer, GeneDx, and BIC, and likely benign by Invitae and Laboratory Corporation of America), Clinvitae (5x), LOVD 3.0 (1x), BIC Database (5x), with unknown clinical importance, classification pending), and Zhejiang University Database (1x). The variant was identified by our laboratory in 1 individual with pancreatic cancer, co-occurring with a pathogenic BRCA2 variant (c.3109C>T, p.Gln1037X); in addition, the variant was identified in UMD-LSDB 2x as 3-UV, co-occurring with a pathogenic BRCA1 variant (c.3181delA, p.Ile1061X), increasing the likelihood that the variant does not have clinical significance. The variant was not identified in Cosmic, MutDB, and ARUP Laboratories. The variant was identified in control databases in 18 of 276992 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). It was observed in the East Asian population in 18 of 18866 chromosomes (freq: 0.001); it was not observed in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, Finnish, and South Asian populations. The p.Pro1150 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
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Comment:
Comment:
This variant is denoted BRCA1 c.3448C>T at the cDNA level, p.Pro1150Ser (P1150S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). Using alternate nomenclature, this variant has been previously published as BRCA1 3567C>T. This variant was observed in individuals with breast cancer, but was also seen in controls (Katagiri 1996, Tang 1999, Belogianni 2004, Jang 2012, Yoon 2016, Zhong 2016, Li 2017, Ryu 2017). A homologous-directed repair assay demonstrated that this variant results in homologous recombination activity similar to the wildtype protein (Lu 2015). BRCA1 Pro1150Ser was observed at an allele frequency of 0.095% (18/18866) in individuals of East Asian ancestry in large population cohorts (Lek 2016). Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro1150Ser occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Pro1150Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Comment:
Variant summary: BRCA1 c.3448C>T (p.Pro1150Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251790 control chromosomes, predominantly at a frequency of 0.0013 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.3448C>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer, without strong evidence for pathogenicity (example, Haffty_2009, Haiman_2013, Liang_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least one co-occurrence with another pathogenic variant(s) have been reported in the UMD database (BRCA1 c.3181delA, p.Ile1061X), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function (example, Lu_2015). The most pronounced variant effect results in approximately 89% of normal homology directed repair (HDR) activity suggestive of a non-significant impact on protein function. Multiple clinical diagnostic laboratories and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 with a predominant consensus as benign/likely benign to include the expert panel. Based on the evidence outlined above, the variant was classified as benign.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
The BRCA1 c.3448C>T variant is predicted to result in the amino acid substitution p.Pro1150Ser. This variant has been reported in patients with breast or ovarian cancer, although pathogenicity was not clearly established (Emi et al. 1998. PubMed ID: 9510469; Yang et al. 2017. PubMed ID: 28664506; Eoh et al. 2017. PubMed ID: 29020732; Li et al. 2019. PubMed ID: 29752822; So et al. 2019. PubMed ID: 30725392). It has been observed in both cases and controls in a study of breast cancer patients (Momozawa et al. 2018. PubMed ID: 30287823) and has been reported as likely benign due to co-occurrence with a pathogenic variant (Lee et al. 2018. PubMed ID: 30415210). This variant has been reported at a frequency of ~0.1% in individuals of East Asian origin in the gnomAD database and is classified as benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/54887/). An internal summary of amino acid substitution prediction programs predicts the p.Pro1150Ser change to be “damaging” (Liu et al. 2016. PMID: 26555599). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain.
Comment:
The BRCA1 p.Pro1150Ser variant was identified in 13 of 4830 proband chromosomes (frequency: 0.003) from Chinese and Korean individuals or families with breast cancer, and in 3 of 1892 control chromosomes (frequency: 0.002) from healthy individuals (Tang 1999, Li 2017 , Jang 2012, Suter 2004, Yang 2017, Yoon 2016). The variant was also identified in dbSNP (ID: rs80357272) as “With other allele”, in ClinVar (classified with conflicting interpretations of pathogenicity; submitters: uncertain significance by Ambry Genetics, CHEO Genetics Diagnostic Laboratory, Laboratory of Molecular Diagnosis of Cancer, GeneDx, and BIC, and likely benign by Invitae and Laboratory Corporation of America), Clinvitae (5x), LOVD 3.0 (1x), BIC Database (5x), with unknown clinical importance, classification pending), and Zhejiang University Database (1x). The variant was identified by our laboratory in 1 individual with pancreatic cancer, co-occurring with a pathogenic BRCA2 variant (c.3109C>T, p.Gln1037X); in addition, the variant was identified in UMD-LSDB 2x as 3-UV, co-occurring with a pathogenic BRCA1 variant (c.3181delA, p.Ile1061X), increasing the likelihood that the variant does not have clinical significance. The variant was not identified in Cosmic, MutDB, and ARUP Laboratories. The variant was identified in control databases in 18 of 276992 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). It was observed in the East Asian population in 18 of 18866 chromosomes (freq: 0.001); it was not observed in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, Finnish, and South Asian populations. The p.Pro1150 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02; http://priors.hci.utah.edu/PRIORS/), AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/), AND minor allele frequency 0.00119 (East Asian), derived from gnomAD v2.1.1 non-cancer (2019-05-13).
Comment:
This variant is denoted BRCA1 c.3448C>T at the cDNA level, p.Pro1150Ser (P1150S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). Using alternate nomenclature, this variant has been previously published as BRCA1 3567C>T. This variant was observed in individuals with breast cancer, but was also seen in controls (Katagiri 1996, Tang 1999, Belogianni 2004, Jang 2012, Yoon 2016, Zhong 2016, Li 2017, Ryu 2017). A homologous-directed repair assay demonstrated that this variant results in homologous recombination activity similar to the wildtype protein (Lu 2015). BRCA1 Pro1150Ser was observed at an allele frequency of 0.095% (18/18866) in individuals of East Asian ancestry in large population cohorts (Lek 2016). Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro1150Ser occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Pro1150Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Comment:
Variant summary: BRCA1 c.3448C>T (p.Pro1150Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251790 control chromosomes, predominantly at a frequency of 0.0013 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.3448C>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer, without strong evidence for pathogenicity (example, Haffty_2009, Haiman_2013, Liang_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least one co-occurrence with another pathogenic variant(s) have been reported in the UMD database (BRCA1 c.3181delA, p.Ile1061X), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function (example, Lu_2015). The most pronounced variant effect results in approximately 89% of normal homology directed repair (HDR) activity suggestive of a non-significant impact on protein function. Multiple clinical diagnostic laboratories and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 with a predominant consensus as benign/likely benign to include the expert panel. Based on the evidence outlined above, the variant was classified as benign.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
The BRCA1 c.3448C>T variant is predicted to result in the amino acid substitution p.Pro1150Ser. This variant has been reported in patients with breast or ovarian cancer, although pathogenicity was not clearly established (Emi et al. 1998. PubMed ID: 9510469; Yang et al. 2017. PubMed ID: 28664506; Eoh et al. 2017. PubMed ID: 29020732; Li et al. 2019. PubMed ID: 29752822; So et al. 2019. PubMed ID: 30725392). It has been observed in both cases and controls in a study of breast cancer patients (Momozawa et al. 2018. PubMed ID: 30287823) and has been reported as likely benign due to co-occurrence with a pathogenic variant (Lee et al. 2018. PubMed ID: 30415210). This variant has been reported at a frequency of ~0.1% in individuals of East Asian origin in the gnomAD database and is classified as benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/54887/). An internal summary of amino acid substitution prediction programs predicts the p.Pro1150Ser change to be “damaging” (Liu et al. 2016. PMID: 26555599). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain.
Comment:
The BRCA1 p.Pro1150Ser variant was identified in 13 of 4830 proband chromosomes (frequency: 0.003) from Chinese and Korean individuals or families with breast cancer, and in 3 of 1892 control chromosomes (frequency: 0.002) from healthy individuals (Tang 1999, Li 2017 , Jang 2012, Suter 2004, Yang 2017, Yoon 2016). The variant was also identified in dbSNP (ID: rs80357272) as “With other allele”, in ClinVar (classified with conflicting interpretations of pathogenicity; submitters: uncertain significance by Ambry Genetics, CHEO Genetics Diagnostic Laboratory, Laboratory of Molecular Diagnosis of Cancer, GeneDx, and BIC, and likely benign by Invitae and Laboratory Corporation of America), Clinvitae (5x), LOVD 3.0 (1x), BIC Database (5x), with unknown clinical importance, classification pending), and Zhejiang University Database (1x). The variant was identified by our laboratory in 1 individual with pancreatic cancer, co-occurring with a pathogenic BRCA2 variant (c.3109C>T, p.Gln1037X); in addition, the variant was identified in UMD-LSDB 2x as 3-UV, co-occurring with a pathogenic BRCA1 variant (c.3181delA, p.Ile1061X), increasing the likelihood that the variant does not have clinical significance. The variant was not identified in Cosmic, MutDB, and ARUP Laboratories. The variant was identified in control databases in 18 of 276992 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). It was observed in the East Asian population in 18 of 18866 chromosomes (freq: 0.001); it was not observed in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, Finnish, and South Asian populations. The p.Pro1150 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients. | Zhang Y | BMC cancer | 2022 | PMID: 35918668 |
| BRCA1 Norway: comparison of classification for BRCA1 germline variants detected in families with suspected hereditary breast and ovarian cancer between different laboratories. | Hovland HN | Familial cancer | 2022 | PMID: 34981296 |
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Integration of functional assay data results provides strong evidence for classification of hundreds of BRCA1 variants of uncertain significance. | Lyra PCM Jr | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 33087888 |
| Prevalence of BRCA1/BRCA2 pathogenic variation in Chinese Han population. | Dong H | Journal of medical genetics | 2021 | PMID: 32467295 |
| Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population. | Jiang Y | BioMed research international | 2020 | PMID: 32879886 |
| Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer. | You Y | Frontiers in oncology | 2020 | PMID: 32211327 |
| Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer. | Kim HK | Journal of human genetics | 2020 | PMID: 31907386 |
| Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. | Gao X | Human mutation | 2020 | PMID: 31825140 |
| Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
| Reinterpretation of BRCA1 and BRCA2 variants of uncertain significance in patients with hereditary breast/ovarian cancer using the ACMG/AMP 2015 guidelines. | So MK | Breast cancer (Tokyo, Japan) | 2019 | PMID: 30725392 |
| Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
| Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
| Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort. | Lee JS | Journal of medical genetics | 2018 | PMID: 30415210 |
| Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
| Prevalence and Spectrum of BRCA1/2 Germline Mutations in Women with Breast Cancer in China Based on Next-Generation Sequencing. | Liang Y | Medical science monitor : international medical journal of experimental and clinical research | 2018 | PMID: 29681614 |
| Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2. | Eoh KJ | Cancer research and treatment | 2018 | PMID: 29020732 |
| Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia. | Yang XR | Breast cancer research and treatment | 2017 | PMID: 28664506 |
| Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing. | Li G | Journal of cancer research and clinical oncology | 2017 | PMID: 28664449 |
| Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea. | Ryu JM | Breast (Edinburgh, Scotland) | 2017 | PMID: 28364669 |
| Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. | Park JS | Cancer research and treatment | 2017 | PMID: 28111427 |
| Clinically Significant Unclassified Variants in BRCA1 and BRCA2 genes among Korean Breast Cancer Patients. | Yoon KA | Cancer research and treatment | 2017 | PMID: 27658390 |
| Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients. | Zhong X | PloS one | 2016 | PMID: 27257965 |
| Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
| Identification of Medically Actionable Secondary Findings in the 1000 Genomes. | Olfson E | PloS one | 2015 | PMID: 26332594 |
| Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population. | Haiman CA | PLoS genetics | 2013 | PMID: 23555315 |
| Spectra of BRCA1 and BRCA2 mutations in Korean patients with breast cancer: the importance of whole-gene sequencing. | Jang JH | Journal of human genetics | 2012 | PMID: 22217648 |
| Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups. | Haffty BG | Annals of oncology : official journal of the European Society for Medical Oncology | 2009 | PMID: 19491284 |
| Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients. | Konstantopoulou I | Breast cancer research and treatment | 2008 | PMID: 17453335 |
| Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans. | Burk-Herrick A | Mammalian genome : official journal of the International Mammalian Genome Society | 2006 | PMID: 16518693 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. | Pavlicek A | Human molecular genetics | 2004 | PMID: 15385441 |
| Characterization of a novel large deletion and single point mutations in the BRCA1 gene in a Greek cohort of families with suspected hereditary breast cancer. | Belogianni I | BMC cancer | 2004 | PMID: 15353005 |
| Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
| BRCA1 and BRCA2 mutations in women from Shanghai China. | Suter NM | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2004 | PMID: 14973102 |
| Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. | Ikeda N | International journal of cancer | 2001 | PMID: 11149425 |
| Prevalence of mutations in the BRCA1 gene among Chinese patients with breast cancer. | Tang NL | Journal of the National Cancer Institute | 1999 | PMID: 10340909 |
| Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers. | Emi M | Japanese journal of cancer research : Gann | 1998 | PMID: 9510469 |
| Mutations in the BRCA1 gene in Japanese breast cancer patients. | Katagiri T | Human mutation | 1996 | PMID: 8723683 |
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Text-mined citations for rs80357272 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.