ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.705A>G (p.Leu235=)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000038.6(APC):c.705A>G (p.Leu235=)
Variation ID: 92349 Accession: VCV000092349.62
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112792505 (GRCh38) [ NCBI UCSC ] 5: 112128202 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Dec 6, 2016 Oct 8, 2024 Feb 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.705A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Leu235= synonymous NM_001127510.3:c.705A>G NP_001120982.1:p.Leu235= synonymous NM_001127511.3:c.676-8774A>G intron variant NM_001354895.2:c.705A>G NP_001341824.1:p.Leu235= synonymous NM_001354896.2:c.705A>G NP_001341825.1:p.Leu235= synonymous NM_001354897.2:c.735A>G NP_001341826.1:p.Leu245= synonymous NM_001354898.2:c.630A>G NP_001341827.1:p.Leu210= synonymous NM_001354899.2:c.646-8774A>G intron variant NM_001354900.2:c.528A>G NP_001341829.1:p.Leu176= synonymous NM_001354901.2:c.528A>G NP_001341830.1:p.Leu176= synonymous NM_001354902.2:c.735A>G NP_001341831.1:p.Leu245= synonymous NM_001354903.2:c.705A>G NP_001341832.1:p.Leu235= synonymous NM_001354904.2:c.630A>G NP_001341833.1:p.Leu210= synonymous NM_001354905.2:c.528A>G NP_001341834.1:p.Leu176= synonymous NM_001354906.2:c.-331A>G 5 prime UTR NC_000005.10:g.112792505A>G NC_000005.9:g.112128202A>G NG_008481.4:g.104985A>G LRG_130:g.104985A>G LRG_130t1:c.705A>G - Protein change
- Other names
- p.L235L:TTA>TTG
- CCDS4107.1:c.705A>G
- NM_000038.6(APC):c.705A>G
- p.Leu235=
- Canonical SPDI
- NC_000005.10:112792504:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00120 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00120
1000 Genomes Project 30x 0.00125
The Genome Aggregation Database (gnomAD) 0.00213
Exome Aggregation Consortium (ExAC) 0.00222
The Genome Aggregation Database (gnomAD), exomes 0.00228
Trans-Omics for Precision Medicine (TOPMed) 0.00230
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00254
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 | ||
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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. |
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APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14938 | 15076 |
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. |
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Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000077993.35 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 20, 2022 | RCV000123677.21 | |
Benign (1) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV000276575.13 | |
Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000679083.38 | |
Benign (1) |
no assertion criteria provided
|
- | RCV001353583.9 | |
Benign (4) |
reviewed by expert panel
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Feb 18, 2023 | RCV002514368.11 |
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. |
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Benign
(Feb 18, 2023)
|
reviewed by expert panel
Method: curation
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Familial adenomatous polyposis 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV003836570.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
The c.705A>G (p.Leu235=) variant in APC is a synonymous (silent) variant that is not predicted to impact splicing by multiple splicing predictors including SpliceAI, VarSEAK … (more)
The c.705A>G (p.Leu235=) variant in APC is a synonymous (silent) variant that is not predicted to impact splicing by multiple splicing predictors including SpliceAI, VarSEAK and MaxEntScan (BP4, BP7). This variant has been observed 3 times in homozygous state in gnomAD 2.1.1 (BS2). The highest population minor allele frequency in the non-cancer population of gnomAD v2.1.1 is 0.004669 in the Finnish population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) threshold (>0.001) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BA1, BS2, BP4, and BP7 (Specification Version 1.0; date of approval: 12/12/2022). (less)
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Benign
(Jan 27, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167020.11
First in ClinVar: Jun 23, 2014 Last updated: Aug 27, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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Likely benign
(Jan 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002069696.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
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Benign
(Mar 17, 2016)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000681844.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
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Benign
(Dec 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV002819250.1
First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023 |
|
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Likely benign
(Jul 24, 2014)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000212748.7
First in ClinVar: Mar 24, 2015 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)
|
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Likely benign
(Feb 09, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805461.1
First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018 |
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Benign
(Sep 20, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000109830.8
First in ClinVar: Jan 23, 2014 Last updated: Aug 27, 2017 |
Number of individuals with the variant: 2
Sex: mixed
|
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Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
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APC-Associated Polyposis Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000451985.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Aug 31, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002527379.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015859.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
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Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550570.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
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Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000252593.12
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
|
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Benign
(Oct 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602537.5
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
|
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Benign
(Feb 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004931021.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
|
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Likely benign
(Aug 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002586065.14
First in ClinVar: Oct 22, 2022 Last updated: Oct 08, 2024 |
Comment:
APC: BP4, BP7, BS1
Number of individuals with the variant: 42
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257028.2
First in ClinVar: Nov 20, 2015 Last updated: Aug 27, 2017 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798801.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808210.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921686.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
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Likely benign
(Oct 10, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000693488.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Carcinoma of colon
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591049.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Leu235Leu variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a … (more)
The p.Leu235Leu variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It has been reported in the UMD (x1) and LOVD (x2) databases. In addition, it is observed as a low frequency variant in the ESP cohort, increasing the likelihood this variant does not have clinical significance. In summary, based on the above information, this variant is predicted benign. (less)
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743904.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951960.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001964968.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APC | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/f6cb4954-a857-4ac2-a4db-5367f1a4f0d3 | - | - | - | - |
Text-mined citations for rs147036141 ...
HelpRecord last updated Oct 08, 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.