Submissions for variant NM_032043.3(BRIP1):c.1171A>G (p.Ile391Val)

gnomAD frequency: 0.00003  dbSNP: rs863224798

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000195653	SCV000255144	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2024-10-31	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 391 of the BRIP1 protein (p.Ile391Val). This variant is not present in population databases (gnomAD no frequency). 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: 216784). 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.
Ambry Genetics	RCV000564729	SCV000666197	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-02	criteria provided, single submitter	clinical testing	The p.I391V variant (also known as c.1171A>G), located in coding exon 8 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1171. The isoleucine at codon 391 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well 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.
Counsyl	RCV000662590	SCV000785217	uncertain significance	Fanconi anemia complementation group J; Ovarian neoplasm	2017-06-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000564729	SCV001349807	uncertain significance	Hereditary cancer-predisposing syndrome	2021-04-30	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with valine at codon 391 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250356 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.
Sema4, Sema4	RCV000564729	SCV002531331	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-10	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV003316112	SCV004019393	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	RCV003316112	SCV005059287	uncertain significance	Familial cancer of breast	2024-01-11	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000195653	SCV005654128	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2024-06-06	criteria provided, single submitter	clinical testing