ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.463C>G (p.Gln155Glu) (rs80357180)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083209 SCV000244366 benign Breast-ovarian cancer, familial 1 2015-08-10 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 = 0.0000389
Invitae RCV001079530 SCV000076627 benign Hereditary breast and ovarian cancer syndrome 2020-10-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162968 SCV000213456 benign Hereditary cancer-predisposing syndrome 2014-11-18 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.
GeneDx RCV000433057 SCV000516831 likely benign not specified 2017-01-20 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758835 SCV000887704 benign not provided 2018-04-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162968 SCV000903496 benign Hereditary cancer-predisposing syndrome 2016-08-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083209 SCV000115283 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083209 SCV000145590 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353810 SCV000591272 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Gln155Glu variant was identified in 1 of 121052 proband chromosomes (frequency: 0.00) from individuals or families with hereditary breast and ovarian cancer (Easton 2007). The variant was also identified in dbSNP (ID: rs#80357180) “With other, untested allele”, LOVD (3X as "Predicted neutral)", ClinVar database, the BIC database (3 X with unknown clinical importance), and UMD (3 X as an unknown variant). The variant was classified as a benign variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). Multiple functional studies have classified the variant as benign (Abkevich 2004, Easton 2007, Lindor 2012, Millot 2012). In addition, the variant was identified with a co-occurring pathogenic BRCA1 variant (p.Arg1443X), increasing the likelihood that the p.Gln155Glu variant does not have clinical significance (Judkins 2005). The p.Gln155 residue is not conserved in mammals and the variant amino acid Glutamic Acid (Glu) is present in cows increasing the likelihood that this variant does not have clinical significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.

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