ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.135-5T>C (rs587781916)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130259 SCV000185103 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-16 criteria provided, single submitter clinical testing The c.135-5T>C intronic variant (also known as IVS3-5T>C) results from a T to C substitution 5 nucleotides upstream from coding exon 3 in the BRCA1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 64000 alleles tested) in our clinical cohort (includes this individual).This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on the acceptor splice site; however, direct evidence is unavailable.Since supporting evidence is limited at this time, the clinical significance ofc.135-5T>Cremains unclear.
Invitae RCV000200745 SCV000253495 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-25 criteria provided, single submitter clinical testing
GeneDx RCV000236507 SCV000292716 uncertain significance not provided 2016-02-16 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.135-5T>C or IVS3-5T>C and consists of a T>C nucleotide substitution at the -5 position of intron 3 of the BRCA1 gene. Using alternate nomenclature, this variant would be defined as BRCA1 254-5T>C. This variant is not predicted to cause abnormal splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 c.135-5T>C was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The thymine (T) nucleotide that is altered is conserved across species. Based on currently available information, it is unclear whether BRCA1 c.135-5T>C is pathogenic or benign. We consider it to be a variant of uncertain significance.
Mendelics RCV000200745 SCV000839315 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000989914 SCV001140646 uncertain significance Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Brotman Baty Institute,University of Washington RCV000989914 SCV001237950 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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