ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4174-8_4174-6del

dbSNP: rs751729752
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000203818 SCV000262342 benign Neurofibromatosis, type 1 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000679389 SCV000568608 likely benign not provided 2020-10-20 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 15060124)
PreventionGenetics, part of Exact Sciences RCV000679389 SCV000806280 likely benign not provided 2014-02-21 criteria provided, single submitter clinical testing
Mendelics RCV000203818 SCV000839146 likely benign Neurofibromatosis, type 1 2018-07-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000679389 SCV001151261 likely benign not provided 2024-07-01 criteria provided, single submitter clinical testing NF1: BP4, BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001579747 SCV002511461 benign not specified 2022-04-19 criteria provided, single submitter clinical testing Variant summary: NF1 c.4111-8_4111-6delGTT alters a 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. A mini-gene assay showed the variant to not impact splicing (Morbidoni_2021). The variant allele was found at a frequency of 0.00046 in 251202 control chromosomes, predominantly at a frequency of 0.00088 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 4.22 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. c.4111-8_4111-6delGTT has been reported in the literature in individuals affected with Neurofibromatosis Type 1, and in one family the variant did not segregate with disease (Morbidoni_2021). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation: three classified as likely benign/benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4 RCV002256122 SCV002527553 likely benign Hereditary cancer-predisposing syndrome 2021-03-30 criteria provided, single submitter curation
Genome-Nilou Lab RCV000203818 SCV002560714 benign Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000203818 SCV002567752 likely benign Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV004558459 SCV003745298 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-28 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001579747 SCV001808378 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000679389 SCV001975760 likely benign not provided no assertion criteria provided clinical testing

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