ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4514+1G>A (rs1279529138)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506844 SCV000604526 pathogenic not specified 2017-02-14 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000722023 SCV000853198 pathogenic Optic nerve glioma 2016-04-14 criteria provided, single submitter clinical testing This is a splice site alteration, in which a G is replaced by an A at the first nucleotide in intron 33.
GeneDx RCV000522042 SCV000617584 pathogenic not provided 2017-08-09 criteria provided, single submitter clinical testing The c.4514+1G>A variant in the NF1 gene has been reported previously in association with neurofibromatosis type 1 (Fahsold et al., 2000; Santoro et al., 2017). This splice site variant destroys the canonical splice donor site in intron 33. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.4514+1G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.4514+1G>A as a pathogenic variant, consistent with a diagnosis of neurofibromatosis type 1 in this individual and his father.
Invitae RCV000547922 SCV000628600 pathogenic Neurofibromatosis, type 1 2017-05-16 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 33 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with neurofibromatosis type 1 (PMID: 10712197). For these reasons, this variant has been classified as Pathogenic.
Yale Center for Mendelian Genomics,Yale University RCV000845193 SCV000987129 likely pathogenic Midaortic syndrome 2018-02-26 no assertion criteria provided literature only

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