ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1831G>A (p.Val611Ile)

gnomAD frequency: 0.00004  dbSNP: rs777741543
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165836 SCV000216583 likely benign Hereditary cancer-predisposing syndrome 2024-03-04 criteria provided, single submitter clinical testing 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000233742 SCV000290991 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 611 of the BRIP1 protein (p.Val611Ile). This variant is present in population databases (rs777741543, gnomAD 0.02%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 186270). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000480949 SCV000566827 uncertain significance not provided 2024-07-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in individuals with ovarian or colorectal cancer (PMID: 28135145, 26315354); This variant is associated with the following publications: (PMID: 28135145, 26315354, 11301010)
Color Diagnostics, LLC DBA Color Health RCV000165836 SCV000684160 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-17 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 611 of the BRIP1 protein. Computational prediction 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 individuals affected with ovarian cancer (PMID: 26315354) or colorectal cancer (PMID: 28135145). This variant has been identified in 3/282802 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.
Counsyl RCV000662932 SCV000785888 uncertain significance Fanconi anemia complementation group J; Ovarian neoplasm 2018-01-04 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003230262 SCV003928122 uncertain significance Familial cancer of breast 2023-03-16 criteria provided, single submitter clinical testing The BRIP1 c.1831G>A (p.Val611Ile) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. The variant was reported in an individual with ovarian cancer (PMID 26315354). To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Myriad Genetics, Inc. RCV003230262 SCV004019386 uncertain significance Familial cancer of breast 2023-02-28 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV003230262 SCV004217064 uncertain significance Familial cancer of breast 2023-07-06 criteria provided, single submitter clinical testing

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