ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1736G>A (p.Arg579His)

gnomAD frequency: 0.00003  dbSNP: rs768224857
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000636129 SCV000757561 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 579 of the BRIP1 protein (p.Arg579His). This variant is present in population databases (rs768224857, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 530325). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRIP1 protein function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV000775419 SCV000909772 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000775419 SCV001173474 likely benign Hereditary cancer-predisposing syndrome 2022-06-14 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV005000414 SCV005623266 uncertain significance not provided 2024-11-21 criteria provided, single submitter clinical testing The BRIP1 c.1736G>A (p.Arg579His) variant has been reported in the published literature in an individual with prostate cancer (PMID: 36922933 (2022)). The frequency of this variant in the general population, 0.0002 (6/30612 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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