ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5075-53C>T (rs8176258)

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Total submissions: 7
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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) RCV000112489 SCV000244612 benign Breast-ovarian cancer, familial 1 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.03166 (European), derived from 1000 genomes (2012-04-30).
Vantari Genetics RCV000210780 SCV000267002 benign Hereditary cancer-predisposing syndrome 2015-11-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000210780 SCV000683250 benign Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000112489 SCV000743381 benign Breast-ovarian cancer, familial 1 2014-10-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112489 SCV000744602 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112489 SCV000145300 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502934 SCV000591576 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 c.5075-53C>T variant is not expected to have clinical significance as it occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in 2 of 148 proband chromosomes (frequency: 0.027) from individuals or families with breast cancer and was present in 2 of 480 control chromosomes (frequency: 0.0.004) from healthy individuals (Cvok 2008, Jara 2006, Pietschmann 2005). This variant was identified in several populations at polymorphic frequencies, including: the 1000 Genomes Project (frequency: 0.015), HAPMAP-CEU (frequency: 0.034), HAP-YRI (frequency: 0.031), and the European American population of the ESP Project (frequency: 0.02). The variant was also listed in dbSNP (ID: rs8176258) “With Uncertain significance allele”, the ClinVar database, the BIC database (20X with no clinical importance and categorized as Class 1: Not pathogenic/low clinical significance), and in UMD (209X as a neutral variant). In the UMD database, the variant was identified with 12 different co-occurring pathogenic BRCA1 variants and 11 different co-occurring pathogenic BRCA2 variants, increasing the likelihood that the c.5075-53C>T variant does not have clinical significance. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.

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