ClinVar Genomic variation as it relates to human health
NM_032043.3(BRIP1):c.3651G>T (p.Trp1217Cys)
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.
Uncertain significance(6); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_032043.3(BRIP1):c.3651G>T (p.Trp1217Cys)
Variation ID: 141402 Accession: VCV000141402.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q23.2 17: 61683395 (GRCh38) [ NCBI UCSC ] 17: 59760756 (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 Apr 29, 2017 May 1, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032043.3:c.3651G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_114432.2:p.Trp1217Cys missense NC_000017.11:g.61683395C>A NC_000017.10:g.59760756C>A NG_007409.2:g.185165G>T LRG_300:g.185165G>T LRG_300t1:c.3651G>T LRG_300p1:p.Trp1217Cys - Protein change
- W1217C
- Other names
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- Canonical SPDI
- NC_000017.11:61683394:C:A
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00010
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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BRIP1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5541 | 5595 |
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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Jul 26, 2023 | RCV000129907.21 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 29, 2024 | RCV000227303.25 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Oct 6, 2020 | RCV000657056.16 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 28, 2022 | RCV000989972.12 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 23, 2024 | RCV003492594.1 |
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. |
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Uncertain significance
(Nov 02, 2016)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000807147.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Fanconi anemia complementation group J
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000896645.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Uncertain significance
(Sep 03, 2019)
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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: SCV000567861.4
First in ClinVar: Apr 29, 2017 Last updated: Jul 09, 2018 |
Comment:
Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this … (more)
Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in an individual with breast cancer (Tung 2016); This variant is associated with the following publications: (PMID: 26976419, 29625052) (less)
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Uncertain significance
(Oct 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600918.2
First in ClinVar: Apr 29, 2017 Last updated: Jan 03, 2022 |
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Uncertain significance
(May 23, 2023)
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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
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000911032.5
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces tryptophan with cysteine at codon 1217 of the BRIP1 protein. Computational prediction tool suggests that this variant may not impact protein … (more)
This missense variant replaces tryptophan with cysteine at codon 1217 of the BRIP1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with breast cancer (PMID: 26976419). This variant has been identified in 2/250810 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Likely benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Fanconi anemia complementation group J
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000291046.11
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
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Uncertain significance
(Jul 26, 2023)
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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
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Ambry Genetics
Accession: SCV000184725.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.W1217C variant (also known as c.3651G>T), located in coding exon 19 of the BRIP1 gene, results from a G to T substitution at nucleotide … (more)
The p.W1217C variant (also known as c.3651G>T), located in coding exon 19 of the BRIP1 gene, results from a G to T substitution at nucleotide position 3651. The tryptophan at codon 1217 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a cohort of 488 patients with breast cancer who were tested with a 25-gene panel test (Tung N et al. J. Clin. Oncol., 2016 May;34:1460-8). This alteration was detected in two different cohorts of Brazilian breast cancer patients (Sandoval RL et al. PLoS One, 2021 Feb;16:e0247363; Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This alteration was also detected in a patient with colorectal cancer who was also found to carry a pathogenic mutation in the MSH2 gene (Ricker CN et al. Cancer, 2017 Oct;123:3732-3743). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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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Likely benign
(Mar 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Molecular Diagnostics Laboratory, Barretos Cancer Hospital
Accession: SCV002320684.1
First in ClinVar: Apr 11, 2022 Last updated: Apr 11, 2022 |
Comment:
ACMG criteria: PM2, PS4_MODERADO, BP4, BP2. *Co-occurrence of pathogenic variant (c.2808_2811del) in BRCA2 gene.
Age: 50-59 years
Sex: female
Geographic origin: Brazil
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Likely benign
(Jan 23, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000839346.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 04, 2024 |
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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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Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. | Guindalini RSC | Scientific reports | 2022 | PMID: 35264596 |
Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis. | Sandoval RL | PloS one | 2021 | PMID: 33606809 |
DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer. | Ricker CN | Cancer | 2017 | PMID: 28640387 |
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer. | Tung N | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2016 | PMID: 26976419 |
Text-mined citations for rs542698396 ...
HelpRecord last updated May 01, 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.