ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4972A>G (p.Ile1658Val) (rs147327414)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000034584 SCV000604460 benign not provided 2017-10-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129642 SCV000184437 benign Hereditary cancer-predisposing syndrome 2015-01-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance,In silico models in agreement (benign)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034584 SCV000043390 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Center for Human Genetics, Inc RCV000168431 SCV000782040 likely benign Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000034584 SCV000519050 benign not provided 2016-07-07 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.
ITMI RCV000121634 SCV000085832 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000345616 SCV000401765 likely benign Neurofibromatosis-Noonan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000168431 SCV000401766 likely benign Neurofibromatosis, type 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000305917 SCV000401767 likely benign Neurofibromatosis, familial spinal 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000360704 SCV000401768 likely benign Café-au-lait macules with pulmonary stenosis 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000121634 SCV000919890 benign not specified 2018-12-05 criteria provided, single submitter clinical testing Variant summary: The variant, NF1 c.4972A>G (p.Ile1658Val) results in a conservative amino acid change located in the CRAL-TRIO lipid binding domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0045 in 277174 control chromosomes, predominantly at a frequency of 0.034 within the Latino subpopulation in the gnomAD database, including 31 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 163.18 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 a benign polymorphism found primarily in populations of Latino origin. The variant, c.4972A>G has been reported in the literature in individuals affected with Neurofibromatosis Type 1, in which a nonsense mutation was reported to co-occur in the patient (Xu _2014), providing supporting evidence for a benign role of the variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven 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 as benign (5X) or likely benign (2X). Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000168431 SCV000219128 benign Neurofibromatosis, type 1 2018-01-12 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000121634 SCV000711706 benign not specified 2016-06-02 criteria provided, single submitter clinical testing p.Ile1679Val in exon 37 of NF1: This variant is not expected to have clinical si gnificance because it has been identified in 3.8% (435/11578) of Latino chromoso mes, including 16 homozygous individuals by the Exome Aggregation Consortium (Ex AC, http://exac.broadinstitute.org; dbSNP rs147327414).
PreventionGenetics RCV000121634 SCV000306274 benign not specified criteria provided, single submitter clinical testing

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