chr17-5514896-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_033004.4(NLRP1):c.4280G>A(p.Arg1427Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,152 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1427P) has been classified as Uncertain significance.
Frequency
Consequence
NM_033004.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP1 | NM_033004.4 | c.4280G>A | p.Arg1427Gln | missense_variant | 17/17 | ENST00000572272.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP1 | ENST00000572272.6 | c.4280G>A | p.Arg1427Gln | missense_variant | 17/17 | 1 | NM_033004.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249516Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135376
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727248
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1427 of the NLRP1 protein (p.Arg1427Gln). This variant is present in population databases (rs184023870, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NLRP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1417285). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at