Submissions for variant NM_001042492.3(NF1):c.7457+5G>A

dbSNP: rs1555536171

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598588	SCV000710731	uncertain significance	not provided	2018-02-27	criteria provided, single submitter	clinical testing	The c.7394+5G>A variant in the NF1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Some in-silico splice prediction models predict that c.7394+5G>A may damage the splice donor site in intron 49, which may cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.7394+5G>A change in this individual is unknown. The c.7394+5G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.7394+5G>A as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000793825	SCV000933201	uncertain significance	Neurofibromatosis, type 1	2024-11-29	criteria provided, single submitter	clinical testing	This sequence change falls in intron 49 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 504409). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV000793825	SCV002561085	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003160067	SCV003854944	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-03-03	criteria provided, single submitter	clinical testing	The c.7394+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 49 in the NF1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.