ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5467+8G>A (rs80358062)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000588816 SCV000210223 uncertain significance not provided 2013-11-29 criteria provided, single submitter clinical testing This variant is denoted BRCA1 IVS22+8G>A or c.5467+8G>A and consists of a G>A nucleotide substitution at the +8 position of intron 22 of the BRCA1 gene. Multiple in silico prediction programs predict this variant to create a cryptic splice site that is used instead of the nearby natural donor site. The splicing defect would add 5 bases to the protein and might lead to a change the reading frame; however, it is near to the end of the protein so the clinical significance is unclear. This variant has not, to our knowledge, been published in the literature as pathogenic or benign and is listed twice in BIC as having unknown significance. BRCA1 c.5467+8G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The intronic base is poorly conserved throughout evolution. Based on the currently available information, we cannot assess whether BRCA1 c.5467+8G>A is a pathogenic variant or a benign polymorphism.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160009 SCV000600422 uncertain significance not specified 2016-12-26 criteria provided, single submitter clinical testing
Invitae RCV000557337 SCV000636042 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588816 SCV000699257 uncertain significance not provided 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5467+8G>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this substitution along with 2/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 2/121404 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant of interest has been reported in affected individuals via publications with limited information (ie, lack of co-occurrence and cosegregation data). Clinical diagnostic laboratories report this variant with conflicting classifications "benign" or "uncertain significance." Therefore, until additional information becomes available, the variant of interest has been classified as a "variant of uncertain significance (VUS)."
Color RCV000776226 SCV000911426 likely benign Hereditary cancer-predisposing syndrome 2016-09-26 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077168 SCV000108965 benign Breast-ovarian cancer, familial 1 2013-04-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077168 SCV000145524 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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