Submissions for variant NM_001042492.3(NF1):c.7190-33TTGT[3]

dbSNP: rs149197458

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000247444	SCV000604517	benign	not specified	2018-07-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000247444	SCV000806311	benign	not specified	2016-04-22	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001290823	SCV000890984	benign	Neurofibromatosis, type 1	2022-10-07	criteria provided, single submitter	clinical testing	The NF1 c.7127-19_7127-8delGTTTGTTTGTTT change has a maximum subpopulation frequency of 3.38% in gnomAD v2.1.1 including 6 homozygotes (https://gnomad.broadinstitute.org/). Algorithms that predict the impact of sequence changes on splicing indicate that this variant does not affect splicing. To our knowledge, this variant has not been reported in individuals with Neurofibromatosis type 1. In summary, this variant meets criteria to be classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000247444	SCV001337821	benign	not specified	2020-01-14	criteria provided, single submitter	clinical testing	Variant summary: NF1 c.7127-19_7127-8del12 (also known as c.7127-19_7127-8delGTTTGTTTGTTT) alters a set of nucleotides 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 0.0025 in 154686 control chromosomes in the gnomAD database, including 4 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.7127-19_7127-8del12 in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2 as benign, 1 as likely benign; and 1 as a VUS). Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001290823	SCV001478987	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001558381	SCV001780316	likely benign	not provided	2020-03-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000247444	SCV001879402	benign	not specified	2021-04-19	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000247444	SCV002047256	benign	not specified	2021-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256183	SCV002530185	likely benign	Hereditary cancer-predisposing syndrome	2021-04-23	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001558381	SCV004009775	benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	NF1: BP4, BS1, BS2