Submissions for variant NM_001042492.3(NF1):c.61-4del

dbSNP: rs551568608

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000263544	SCV000401669	likely benign	Neurofibromatosis, type 1	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000321032	SCV000401670	likely benign	Café-au-lait macules with pulmonary stenosis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000377934	SCV000401671	likely benign	Neurofibromatosis, familial spinal	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000267272	SCV000401672	likely benign	Neurofibromatosis-Noonan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000506771	SCV000604506	benign	not specified	2016-11-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589681	SCV000696401	benign	not provided	2017-08-09	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.61-4delT variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign 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 316/77450 control chromosomes from ExAC, predominantly observed in the European (Finnish) subpopulation at a frequency of 0.016349 (79/4832). This frequency is about 78 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 European (Finnish) origin. One patient with neurofibromatosis type 1 carried this variant along with another likely pathogenic splice mutation (c.1642-2A>G), indicating that the variant was not the cause of disease (Mattocks_JMG_2004). In addition, one clinical diagnostic laboratory has classified this variant as likely benign. Taken together, this variant is classified as benign.
GeneDx	RCV000589681	SCV000714113	likely benign	not provided	2021-04-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 15060124, 18592002)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000263544	SCV001479092	likely benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Invitae	RCV000263544	SCV002407936	benign	Neurofibromatosis, type 1	2021-04-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002255365	SCV002527646	benign	Hereditary cancer-predisposing syndrome	2020-10-26	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000506771	SCV002550885	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000263544	SCV002561456	likely benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589681	SCV002563397	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	NF1: BP4, BS1
Ambry Genetics	RCV002356443	SCV002661361	benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2020-07-14	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000589681	SCV001744731	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000589681	SCV001807916	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000506771	SCV001966182	benign	not specified		no assertion criteria provided	clinical testing