ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3267G>C (p.Trp1089Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.3267G>C (p.Trp1089Cys)
Variation ID: 432801 Accession: VCV000432801.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117611708 (GRCh38) [ NCBI UCSC ] 7: 117251762 (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 Sep 28, 2017 Jul 7, 2024 Mar 14, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3267G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Trp1089Cys missense NC_000007.14:g.117611708G>C NC_000007.13:g.117251762G>C NG_016465.4:g.150925G>C NG_056128.2:g.4762G>C LRG_663:g.150925G>C LRG_663t1:c.3267G>C LRG_663p1:p.Trp1089Cys - Protein change
- W1089C
- Other names
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- Canonical SPDI
- NC_000007.14:117611707:G:C
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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
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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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CFTR | - | - |
GRCh38 GRCh37 |
3736 | 5066 | |
LOC111674472 | - | - | - | GRCh38 | - | 390 |
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Mar 14, 2024 | RCV000498926.14 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Feb 25, 2020 | RCV000766815.14 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Sep 5, 2021 | RCV001275773.13 |
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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Uncertain significance
(May 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000590567.3
First in ClinVar: Aug 20, 2017 Last updated: Apr 17, 2019 |
Comment:
The W1089C variant in the CFTR gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The W1089C variant in the CFTR gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The W1089C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The W1089C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret W1089C as a variant of uncertain significance. (less)
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Uncertain significance
(Feb 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001471760.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The CFTR c.3267G>C; p.Trp1089Cys variant (rs150020260), to our knowledge, is not reported in the medical literature in association with disease, but is reported in ClinVar … (more)
The CFTR c.3267G>C; p.Trp1089Cys variant (rs150020260), to our knowledge, is not reported in the medical literature in association with disease, but is reported in ClinVar (Variation ID: 432801). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The tryptophan at codon 1089 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Trp1089Cys variant is uncertain at this time. (less)
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Uncertain significance
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027493.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Uncertain significance
(Jan 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601094.2
First in ClinVar: Sep 28, 2017 Last updated: Jan 01, 2022 |
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Uncertain significance
(Oct 17, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002607042.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.W1089C variant (also known as c.3267G>C), located in coding exon 20 of the CFTR gene, results from a G to C substitution at nucleotide … (more)
The p.W1089C variant (also known as c.3267G>C), located in coding exon 20 of the CFTR gene, results from a G to C substitution at nucleotide position 3267. The tryptophan at codon 1089 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Mar 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004020674.2
First in ClinVar: Jul 29, 2023 Last updated: Jul 07, 2024 |
Comment:
Variant summary: CFTR c.3267G>C (p.Trp1089Cys) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded … (more)
Variant summary: CFTR c.3267G>C (p.Trp1089Cys) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251132 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3267G>C in the literature in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28152038, 25880441). ClinVar contains an entry for this variant (Variation ID: 432801). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Cystic Fibrosis
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001461258.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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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Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels. | LaDuca H | PloS one | 2017 | PMID: 28152038 |
Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk. | Lim RM | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 25880441 |
Text-mined citations for rs150020260 ...
HelpRecord last updated Jul 29, 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.