Submissions for variant NM_001042492.3(NF1):c.479+5G>C

dbSNP: rs1567818033

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002036586	SCV002317607	likely pathogenic	Neurofibromatosis, type 1	2022-02-18	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant has been observed in individual(s) with NF1-related conditions (PMID: 17311297, 32552793). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the c.479+5 nucleotide in the NF1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 23758643, 27322474). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 4a and introduces a premature termination codon (PMID: 17311297). The resulting mRNA is expected to undergo nonsense-mediated decay.