1-247421341-G-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5BP4BA1
The NM_001243133.2(NLRP3):c.278-1889G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,816 control chromosomes in the GnomAD database, including 25,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).
Frequency
Genomes: 𝑓 0.58 ( 25408 hom., cov: 30)
Consequence
NLRP3
NM_001243133.2 intron
NM_001243133.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.24
Genes affected
NLRP3 (HGNC:16400): (NLR family pyrin domain containing 3) This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NLRP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. The SARS-CoV 3a protein, a transmembrane pore-forming viroporin, has been shown to activate the NLRP3 inflammasome via the formation of ion channels in macrophages. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, neonatal-onset multisystem inflammatory disease (NOMID), keratoendotheliitis fugax hereditarian, and deafness, autosomal dominant 34, with or without inflammation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PP5
Variant 1-247421341-G-C is Pathogenic according to our data. Variant chr1-247421341-G-C is described in ClinVar as [Likely_risk_allele]. Clinvar id is 2687869.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9). . Strength limited to SUPPORTING due to the PP5.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NLRP3 | NM_001243133.2 | c.278-1889G>C | intron_variant | Intron 2 of 9 | ENST00000336119.8 | NP_001230062.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP3 | ENST00000336119.8 | c.278-1889G>C | intron_variant | Intron 2 of 9 | 1 | NM_001243133.2 | ENSP00000337383.4 |
Frequencies
GnomAD3 genomes AF: 0.576 AC: 87379AN: 151698Hom.: 25395 Cov.: 30
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.576 AC: 87436AN: 151816Hom.: 25408 Cov.: 30 AF XY: 0.578 AC XY: 42856AN XY: 74200
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ClinVar
Significance: Likely risk allele
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Long COVID-19 Pathogenic:1
-
DECIPHERD-UDD, Universidad del Desarrollo
Significance: Likely risk allele
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at