Submissions for variant NM_001042492.3(NF1):c.1845+13A>T

gnomAD frequency: 0.01016  dbSNP: rs17885739

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000220325	SCV000269446	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	1845+13A>T in intron 16 of NF1: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 3.0% (131/4384) of African American chromosomes f rom a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wash ington.edu/EVS; dbSNP rs17885739).
PreventionGenetics, part of Exact Sciences	RCV000220325	SCV000306241	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000680355	SCV000528764	benign	not provided	2016-11-10	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000680355	SCV000604471	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000220325	SCV001448480	benign	not specified	2020-11-16	criteria provided, single submitter	clinical testing	Variant summary: NF1 c.1845+13A>T 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. 4/4 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 0.0023 in 249728 control chromosomes in the gnomAD database, including 9 homozygotes. The observed variant frequency is approximately 11 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.1845+13A>T in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Two 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. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054385	SCV002435823	benign	Neurofibromatosis, type 1	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002054385	SCV002560968	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316184	SCV004016419	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000680355	SCV005253767	benign	not provided		criteria provided, single submitter	not provided