Submissions for variant NM_032043.3(BRIP1):c.94-4A>G

gnomAD frequency: 0.00001  dbSNP: rs765154059

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000569792	SCV000661536	likely benign	Hereditary cancer-predisposing syndrome	2022-01-11	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.
Color Diagnostics, LLC DBA Color Health	RCV000569792	SCV000689422	likely benign	Hereditary cancer-predisposing syndrome	2016-12-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001420740	SCV001623078	likely benign	not specified	2021-04-16	criteria provided, single submitter	clinical testing	Variant summary: BRIP1 c.94-4A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2e-05 in 251268 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.94-4A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001483905	SCV001688312	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-12-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004791580	SCV005405228	likely benign	Familial cancer of breast	2024-08-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV004791580	SCV005916037	likely benign	Familial cancer of breast	2022-11-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004732947	SCV005347912	likely benign	BRIP1-related disorder	2024-06-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).