Submissions for variant NM_032043.3(BRIP1):c.3336T>C (p.Asp1112=)

gnomAD frequency: 0.00007  dbSNP: rs369843642

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000213752	SCV000273515	likely benign	Hereditary cancer-predisposing syndrome	2015-01-20	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	RCV000230206	SCV000291041	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-01-24	criteria provided, single submitter	clinical testing
Counsyl	RCV000409082	SCV000490021	likely benign	Fanconi anemia complementation group J	2016-10-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000410201	SCV000490022	likely benign	Ovarian neoplasm	2016-10-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000213752	SCV000537483	likely benign	Hereditary cancer-predisposing syndrome	2015-07-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781176	SCV000919055	likely benign	not specified	2018-06-15	criteria provided, single submitter	clinical testing	Variant summary: BRIP1 c.3336T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was reported in 13/276782 control chromosomes in gnomad, with the highest frequency being East Asian (9/18866), which is 7 fold higher than the maximal expected frequency for a pathogenic variant in BRIP1, evidence for the benign nature of this variant. To our knowledge, no occurrence of c.3336T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx	RCV001618349	SCV001844725	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001618349	SCV002046272	likely benign	not provided	2022-04-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000213752	SCV002533686	likely benign	Hereditary cancer-predisposing syndrome	2021-12-01	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV003316200	SCV004019305	benign	Familial cancer of breast	2023-02-27	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
CeGaT Center for Human Genetics Tuebingen	RCV001618349	SCV004703268	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	BRIP1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV004541346	SCV004760306	likely benign	BRIP1-related disorder	2020-08-06	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).