chr17-5514863-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033004.4(NLRP1):c.4313G>A(p.Arg1438Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_033004.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NLRP1 | NM_033004.4 | c.4313G>A | p.Arg1438Gln | missense_variant | 17/17 | ENST00000572272.6 | NP_127497.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP1 | ENST00000572272.6 | c.4313G>A | p.Arg1438Gln | missense_variant | 17/17 | 1 | NM_033004.4 | ENSP00000460475 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000460 AC: 70AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000200 AC: 50AN: 249518Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135386
GnomAD4 exome AF: 0.000315 AC: 461AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000298 AC XY: 217AN XY: 727246
GnomAD4 genome AF: 0.000460 AC: 70AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 07, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1438 of the NLRP1 protein (p.Arg1438Gln). This variant is present in population databases (rs201167590, gnomAD 0.1%). 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: 502755). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 27, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | May 10, 2022 | - - |
NLRP1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 08, 2023 | The NLRP1 c.4313G>A variant is predicted to result in the amino acid substitution p.Arg1438Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-5418183-C-T), which may be too common to be an unreported disease-causing variant. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at