ClinVar Miner

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

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Total submissions: 10
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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
Invitae RCV001083508 SCV000253214 benign Neurofibromatosis, type 1 2019-12-31 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.
PreventionGenetics,PreventionGenetics RCV000679396 SCV000806290 likely benign not provided 2017-02-20 criteria provided, single submitter clinical testing
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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000781665 SCV001159841 likely benign not specified 2019-01-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001126127 SCV001285285 uncertain significance Café-au-lait macules with pulmonary stenosis 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001126128 SCV001285286 uncertain significance Neurofibromatosis, familial spinal 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001083508 SCV001285287 uncertain significance Neurofibromatosis, type 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001126129 SCV001285288 uncertain significance Neurofibromatosis-Noonan syndrome 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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