Submissions for variant NM_007294.3(BRCA1):c.4097-10G>A (rs80358057)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112252	SCV001161514	benign	Breast-ovarian cancer, familial 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 = 0.000573
GeneDx	RCV000159886	SCV000209968	benign	not specified	2014-09-17	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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000724122	SCV000225366	uncertain significance	not provided	2014-07-09	criteria provided, single submitter	clinical testing
Invitae	RCV001080607	SCV000289792	benign	Hereditary breast and ovarian cancer syndrome	2020-12-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000112252	SCV000489057	likely benign	Breast-ovarian cancer, familial 1	2016-08-09	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000580105	SCV000683150	likely benign	Hereditary cancer-predisposing syndrome	2015-07-30	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000724122	SCV000887686	likely benign	not provided	2018-04-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000159886	SCV001360562	benign	not specified	2020-11-12	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.4097-10G>A alters a 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. Consistent with this, one study report that the variant had no apparent effect on mRNA splicing (Rodriguez-Balada_2016). The variant allele was found at a frequency of 1.6e-05 in 243770 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4097-10G>A has been reported in the literature in individuals undergoing genetic testing (Judkins_2005, Rodriguez-Balada_2016). However, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Five other ClinVar submitters including an expert panel (ENIGMA) classified the variant as likely benign or benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001289733	SCV001477711	likely benign	none provided	2020-04-01	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112252	SCV000144973	uncertain significance	Breast-ovarian cancer, familial 1	2002-05-29	no assertion criteria provided	clinical testing