Submissions for variant NM_001042492.3(NF1):c.3198-4T>C

gnomAD frequency: 0.00387  dbSNP: rs587782218

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130902	SCV000185811	likely benign	Hereditary cancer-predisposing syndrome	2015-08-29	criteria provided, single submitter	clinical testing	Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Other data supporting benign classification
Labcorp Genetics (formerly Invitae), Labcorp	RCV000196712	SCV000252680	benign	Neurofibromatosis, type 1	2025-02-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000589461	SCV000525962	benign	not provided	2018-01-23	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.
Genetic Services Laboratory, University of Chicago	RCV000433877	SCV000595973	likely benign	not specified	2017-05-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589461	SCV000696392	benign	not provided	2017-08-16	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.3198-4T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 283/181400 control chromosomes in gnomAD, predominantly observed in the African subpopulation at a frequency of 0.014668 (253/17248). This frequency is about 70 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000196712	SCV000781975	uncertain significance	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130902	SCV002527496	benign	Hereditary cancer-predisposing syndrome	2020-10-26	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000589461	SCV002545908	benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	NF1: BS1, BS2
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000433877	SCV002774033	benign	not specified	2022-02-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004558337	SCV005048157	likely benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2019-07-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.