chr1-247434269-C-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001243133.2(NLRP3):c.2488C>A(p.Leu830Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000165 in 1,614,178 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L830V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001243133.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP3 | NM_001243133.2 | c.2488C>A | p.Leu830Ile | missense_variant | 6/10 | ENST00000336119.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP3 | ENST00000336119.8 | c.2488C>A | p.Leu830Ile | missense_variant | 6/10 | 1 | NM_001243133.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000861 AC: 131AN: 152234Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000270 AC: 68AN: 251394Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135868
GnomAD4 exome AF: 0.0000924 AC: 135AN: 1461826Hom.: 0 Cov.: 36 AF XY: 0.0000756 AC XY: 55AN XY: 727216
GnomAD4 genome AF: 0.000860 AC: 131AN: 152352Hom.: 0 Cov.: 34 AF XY: 0.000940 AC XY: 70AN XY: 74504
ClinVar
Submissions by phenotype
Cryopyrin associated periodic syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
NLRP3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 23, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2021 | This variant is associated with the following publications: (PMID: 32529290) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at