ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4410A>T (p.Glu1470Asp) (rs80357075)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120257 SCV000108679 likely benign not specified 2018-03-02 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.
Ambry Genetics RCV000131557 SCV000186560 benign Hereditary cancer-predisposing syndrome 2015-03-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724288 SCV000225889 uncertain significance not provided 2016-01-11 criteria provided, single submitter clinical testing
Invitae RCV001083415 SCV000254987 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-11 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131557 SCV000688501 likely benign Hereditary cancer-predisposing syndrome 2016-07-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000120257 SCV000699148 likely benign not specified 2018-03-08 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4410A>T (p.Glu1470Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 246024 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (2e-05 vs 1e-03), allowing no conclusion about variant significance. The variant, c.4410A>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Borg_2010, Dutil_2012, Judkins_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.3922G>T, p.Glu1308X - 3 separate individuals), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Woods_2016). Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000724288 SCV001133584 likely benign not provided 2019-07-08 criteria provided, single submitter clinical testing
ITMI RCV000120257 SCV000084409 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000077572 SCV000109375 benign Breast-ovarian cancer, familial 1 2010-09-22 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077572 SCV000145087 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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