Submissions for variant NM_007294.4(BRCA1):c.301+7G>A

gnomAD frequency: 0.00006  dbSNP: rs80358113

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031080	SCV001161508	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-06-18	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 9.89E-13
GeneDx	RCV000168481	SCV000209904	benign	not specified	2014-06-24	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.
Invitae	RCV001086785	SCV000252814	benign	Hereditary breast ovarian cancer syndrome	2021-12-13	criteria provided, single submitter	clinical testing
Counsyl	RCV000031080	SCV000488102	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-12-28	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000579925	SCV000683078	likely benign	Hereditary cancer-predisposing syndrome	2015-07-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759515	SCV000888882	benign	not provided	2018-06-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000168481	SCV000918797	benign	not specified	2021-07-07	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.301+7G>A 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. At least two publication reports experimental evidence evaluating an impact on splicing. These results showed no damaging effect of this variant (Steffensen_2014, Houdayer_2012). The variant allele was found at a frequency of 9.5e-05 in 251608 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (9.5e-05 vs 0.001), allowing no conclusion about variant significance. c.301+7G>A has been reported in the literature in individuals affected with Breast and Ovarian Cancer (Konstantopoulou_2008, Ratajska_2014, Kluska_2015). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Six ClinVar submitters (evaluation after 2014) cite the variant as benign (4x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000759515	SCV001151341	benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory,University of Chicago	RCV000168481	SCV002072390	likely benign	not specified	2019-04-23	criteria provided, single submitter	clinical testing
Sema4,Sema4	RCV000579925	SCV002538168	likely benign	Hereditary cancer-predisposing syndrome	2021-04-11	criteria provided, single submitter	curation
Sharing Clinical Reports Project (SCRP)	RCV000031080	SCV000053676	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2011-03-14	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031080	SCV000144958	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Brotman Baty Institute,University of Washington	RCV000031080	SCV001238612	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000168481	SCV002551062	benign	not specified	2022-02-07	no assertion criteria provided	clinical testing