Submissions for variant NM_032043.3(BRIP1):c.1935+7T>C

gnomAD frequency: 0.00004  dbSNP: rs201024366

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080941	SCV000290995	benign	Familial cancer of breast; Fanconi anemia complementation group J	2025-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000421160	SCV000512422	benign	not specified	2015-07-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000445956	SCV000537445	likely benign	Hereditary cancer-predisposing syndrome	2015-10-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000585911	SCV000699679	benign	not provided	2017-05-15	criteria provided, single submitter	clinical testing	Variant summary: The BRIP1 c.1935+7T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 12/121040 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.001388 (12/8646). This frequency is about 22 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000585911	SCV000889201	likely benign	not provided	2018-06-06	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004786625	SCV005403956	likely benign	Familial cancer of breast	2024-08-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
PreventionGenetics, part of Exact Sciences	RCV004541458	SCV004759628	likely benign	BRIP1-related disorder	2020-12-23	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).