Submissions for variant NM_007294.4(BRCA1):c.671-8A>G

gnomAD frequency: 0.00003  dbSNP: rs80358144

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123888	SCV000167233	benign	not specified	2013-12-30	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087483	SCV000252822	benign	Hereditary breast ovarian cancer syndrome	2025-01-06	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580371	SCV000683345	benign	Hereditary cancer-predisposing syndrome	2016-10-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588347	SCV000699288	benign	not provided	2016-03-26	criteria provided, single submitter	clinical testing	Variant Summary: The c.671-8A>G variant involves the alteration of a non-conserved nucleotide resulting in an intronic change. This variant is located at a position that is not widely known to affect splicing, 3/5 splicing prediction programs via Alamut predict no significant effect on splicing, and mutation taster predicts the variant to be a polymorphism. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.012%, predominantly observed in the East Asian subpopulation at a frequency of 0.18%. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in BRCA1 (0.10%), suggesting this is a benign polymorphism found primarily in population(s) of East Asian origin. The variant has been reported in multiple databases to co-occur in individuals with pathogenic BRCA1 variants including two patients with c.2296_2297delAG, p.Ser766X (UMD), one patient with c.68_69delAG, p.Glu23ValfsX17 (UMD), and one patient with c.188T>A, p.Leu63Ter (BIC). Taken together, the multiple co-occurrences with pathogenic variants along with the intronic nature of the variant and the relatively high frequency in the East Asian population, this variant was classified as Benign.
Counsyl	RCV000112769	SCV000785272	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2017-06-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000112769	SCV001284087	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2017-05-04	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genetic Services Laboratory, University of Chicago	RCV000123888	SCV002072426	uncertain significance	not specified	2019-04-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580371	SCV002537887	likely benign	Hereditary cancer-predisposing syndrome	2022-01-06	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000123888	SCV004026808	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000112769	SCV004836880	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-11-30	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112769	SCV000145661	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000588347	SCV001552352	uncertain significance	not provided		no assertion criteria provided	clinical testing