ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.6084+8C>G (rs182709912)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000679403 SCV000528198 likely benign not provided 2018-04-19 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.
Integrated Genetics/Laboratory Corporation of America RCV000215739 SCV000919883 benign not specified 2018-08-03 criteria provided, single submitter clinical testing Variant summary: NF1 c.6084+8C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0014 in 277138 control chromosomes (gnomAD). The observed variant frequency is approximately 6.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Neurofibromatosis Type 1 phenotype (0.00021), strongly suggesting that the variant is benign. c.6084+8C>G has been reported in the literature in an individual affected with Neurofibromatosis Type 1, however, it was found in co-occurrence with a pathogenic NF1 variant (c.1318 C>T (R440X)), providing supporting evidence for a benign role (Mattocks 2004). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000195559 SCV000252688 benign Neurofibromatosis, type 1 2018-01-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000215739 SCV000269459 benign not specified 2014-11-24 criteria provided, single submitter clinical testing 6147+8C>G in intron 41 of NF1: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 0.3% (27/8600) of European American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS; dbSNP rs182709912).
PreventionGenetics RCV000215739 SCV000306280 likely benign not specified criteria provided, single submitter clinical testing
PreventionGenetics RCV000679403 SCV000806301 likely benign not provided 2014-02-21 criteria provided, single submitter clinical testing

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