Submissions for variant NM_001042492.3(NF1):c.3871-4G>C

gnomAD frequency: 0.00001  dbSNP: rs558421445

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000221113	SCV000274144	likely benign	Hereditary cancer-predisposing syndrome	2016-01-19	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Other data supporting benign classification
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081500	SCV000628553	likely benign	Neurofibromatosis, type 1	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000681157	SCV000808615	likely benign	not provided	2018-03-14	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001081500	SCV001479198	likely benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818522	SCV002068123	uncertain significance	not specified	2020-04-28	criteria provided, single submitter	clinical testing	DNA sequence analysis of the NF1 gene demonstrated a sequence change in intron 28, c.3871-4G>C. This sequence change has been described in the gnomAD database with a low population frequency of 0.002 (dbSNP rs558421445). This sequence change is not clearly predicted to have a deleterious effect on splicing based on in silico splice prediction programs. This change does not appear to have been previously described in patients with NF1-related disorders and has also not been described as a known benign sequence change in the NF1 gene. Due to the lack of sufficient evidences, the clinical and functional significance of this sequence change is not known at present and its contribution to this patient's disease phenotype cannot definitively be determined.
Sema4, Sema4	RCV000221113	SCV002527537	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-26	criteria provided, single submitter	curation
Ambry Genetics	RCV002354617	SCV002620049	likely benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2020-10-14	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.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000221113	SCV005205754	likely benign	Hereditary cancer-predisposing syndrome	2024-06-11	criteria provided, single submitter	clinical testing