ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4675+3A>G (rs80358082)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164653 SCV000215318 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-22 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000463988 SCV000549316 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-08-18 criteria provided, single submitter clinical testing This sequence change falls in intron 14 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503121 SCV000591533 uncertain significance not specified 2015-06-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000503121 SCV000918708 uncertain significance not specified 2017-09-12 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4675+3A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 3/5 splice prediction tools predict significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 121176 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS), until additional information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985423 SCV001133594 uncertain significance not provided 2019-02-14 criteria provided, single submitter clinical testing

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