ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4986C>T (p.Asn1662=) (rs140994965)

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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 RCV000164013 SCV000214618 likely benign Hereditary cancer-predisposing syndrome 2014-07-07 criteria provided, single submitter clinical testing
GeneDx RCV000679396 SCV000527580 likely benign not provided 2018-03-30 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 RCV000781665 SCV000919881 benign not specified 2018-03-28 criteria provided, single submitter clinical testing Variant summary: NF1 c.4986C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 0.0001191 in 277132 control chromosomes (gnomAD). The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 8-folds higher than 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 a benign polymorphism found primarily in population(s) of Ashkenazi Jewish origin. To our knowledge, no occurrence of c.4986C>T in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "benign." Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000200119 SCV000253214 benign Neurofibromatosis, type 1 2018-01-08 criteria provided, single submitter clinical testing
PreventionGenetics RCV000679396 SCV000806290 likely benign not provided 2017-02-20 criteria provided, single submitter clinical testing

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