17-31327637-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP2BP4_ModerateBP6BS2_Supporting
The NM_001042492.3(NF1):āc.5407A>Gā(p.Ile1803Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1803M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.5407A>G | p.Ile1803Val | missense_variant | 38/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.5344A>G | p.Ile1782Val | missense_variant | 37/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.5407A>G | p.Ile1803Val | missense_variant | 38/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152082Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251416Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135878
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727248
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74414
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jul 15, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 12, 2022 | Observed in individuals with a personal or family history including thyroid cancer (Yehia et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29684080) - |
Neurofibromatosis, type 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2015 | Insufficient or conflicting evidence;In silico models in agreement (benign);Rarity in general population databases (dbsnp, esp, 1000 genomes) - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at