ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3496+19T>C

gnomAD frequency: 0.00673  dbSNP: rs9890283
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000253884 SCV000306257 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000680331 SCV000518995 benign not provided 2018-01-02 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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660036 SCV000781987 likely benign Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000680331 SCV001158610 benign not provided 2023-11-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000253884 SCV001338020 benign not specified 2020-01-06 criteria provided, single submitter clinical testing Variant summary: NF1 c.3496+19T>C 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 0.0017 in 250870 control chromosomes in the gnomAD database, including 2 homozygotes. The observed variant frequency is approximately 677.6 fold the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3496+19T>C in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating an impact on protein function have been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000660036 SCV002371818 benign Neurofibromatosis, type 1 2024-02-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000660036 SCV002560672 benign Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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