Submissions for variant NM_001042492.3(NF1):c.*4T>C

gnomAD frequency: 0.00003  dbSNP: rs201044568

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163803	SCV000214386	benign	Hereditary cancer-predisposing syndrome	2015-06-28	criteria provided, single submitter	clinical testing	Other data supporting benign classification;Other strong data supporting benign classification
Labcorp Genetics (formerly Invitae), Labcorp	RCV000196409	SCV000252674	benign	Neurofibromatosis, type 1	2015-08-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000374635	SCV000401817	likely benign	Café-au-lait macules with pulmonary stenosis	2017-04-27	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000196409	SCV000401818	likely benign	Neurofibromatosis, type 1	2017-04-27	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000315760	SCV000401819	likely benign	Neurofibromatosis-Noonan syndrome	2017-04-27	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000372677	SCV000401820	likely benign	Neurofibromatosis, familial spinal	2017-04-27	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genetic Services Laboratory, University of Chicago	RCV000499461	SCV000595978	likely benign	not specified	2016-06-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000499461	SCV001158763	benign	not specified	2019-04-19	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000499461	SCV001365938	benign	not specified	2018-12-28	criteria provided, single submitter	clinical testing	c.*4T>C in exon 58 of NF1: This variant is not expected to have clinical significance because it has been identified in 2.07% (341/16504) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201044568).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000196409	SCV001479298	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000499461	SCV001572453	benign	not specified	2021-04-04	criteria provided, single submitter	clinical testing	Variant summary: NF1 c.*4T>C is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0025 in 251374 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 12 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 benign. To our knowledge, no occurrence of c.*4T>C in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have 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 benign (n=5)/likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001553426	SCV001774290	likely benign	not provided	2024-10-25	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Genome-Nilou Lab	RCV000196409	SCV002561384	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000163803	SCV005045412	benign	Hereditary cancer-predisposing syndrome	2024-02-20	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001553426	SCV005214622	likely benign	not provided		criteria provided, single submitter	not provided