ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4110+4T>C

gnomAD frequency: 0.00002  dbSNP: rs587781700
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129868 SCV000184685 uncertain significance Hereditary cancer-predisposing syndrome 2014-05-23 criteria provided, single submitter clinical testing The c.4110+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 30 in the NF1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 55000 alleles tested) in our clinical cohort. Based on nucleotide sequence alignment, thisnucleotide position is well conserved in available vertebrate species.Using the BDGP and ESEfinder splice site prediction tools, this alteration does not have any significant effect on the native splice donor sites; however, direct evidence is unavailable.Since supporting evidence is limited at this time, the clinical significance ofc.4110+4T>Cremains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000632358 SCV000753536 likely benign Neurofibromatosis, type 1 2025-01-22 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000632358 SCV002560384 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002321615 SCV002632459 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-08-12 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.
Genetic Services Laboratory, University of Chicago RCV003150949 SCV003839766 uncertain significance not specified 2022-04-28 no assertion criteria provided clinical testing DNA sequence analysis of the NF1 gene demonstrated a sequence change in intron 30, c.4110+4T>C. This sequence change has been described in the gnomAD database with a frequency of 0.033% in the East ASian subpopulation (dbSNP rs587781700). This sequence change is not 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 individuals with NF1-related disorders. It is possible that this sequence change represents a benign sequence change in the NF1 gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined

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