Submissions for variant NM_007294.4(BRCA1):c.4186-10G>A

dbSNP: rs80358172

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000589275	SCV000210170	likely benign	not provided	2019-07-02	criteria provided, single submitter	clinical testing	In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 18627636, 16267036, 25561518, 26269718, 28222693, 29280214)
Genetic Services Laboratory, University of Chicago	RCV000212182	SCV000593679	uncertain significance	not specified	2016-08-19	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212182	SCV000605869	benign	not specified	2020-10-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589275	SCV000699117	benign	not provided	2016-04-22	criteria provided, single submitter	clinical testing	Variant summary: The c.4186-10G>A in BRCA1 gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC, mainly in individuals of East Asian descent at frequency of 0.17%, including one homozygous occurrence. The observed frequency exceeds the maximum expected allele frequency for a pathogenic BRCA1 variant, suggesting that it is a polymorphism. The fact that c.4186-10G>A has been reported to co-occur with two different deleterious mutation in BRCA1 gene (c.3700_3704delGTAAA and c.3759_3760delTA) suggests a non-disease causing nature of this variant. In addition, the variant has been reported as Polymorphismin published reports (Soumittra, 2009). Taken together, this variant has been classified as Benign.
Counsyl	RCV000112287	SCV000785402	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-07-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771225	SCV000903320	likely benign	Hereditary cancer-predisposing syndrome	2017-08-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589275	SCV001472093	likely benign	not provided	2020-08-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001514091	SCV001721844	benign	Hereditary breast ovarian cancer syndrome	2025-01-22	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001514091	SCV002025942	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000771225	SCV002538270	benign	Hereditary cancer-predisposing syndrome	2021-04-30	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212182	SCV002760927	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149707	SCV003838727	likely benign	Breast and/or ovarian cancer	2021-11-29	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112287	SCV000145019	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000112287	SCV000297608	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2010-09-13	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004554673	SCV004755541	likely benign	BRCA1-related disorder	2019-04-16	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).