rs56710146
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001243133.2(NLRP3):c.423C>T(p.Tyr141Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,922 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001243133.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NLRP3 | NM_001243133.2 | c.423C>T | p.Tyr141Tyr | synonymous_variant | Exon 4 of 10 | ENST00000336119.8 | NP_001230062.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP3 | ENST00000336119.8 | c.423C>T | p.Tyr141Tyr | synonymous_variant | Exon 4 of 10 | 1 | NM_001243133.2 | ENSP00000337383.4 |
Frequencies
GnomAD3 genomes AF: 0.00623 AC: 947AN: 151982Hom.: 13 Cov.: 30
GnomAD3 exomes AF: 0.00162 AC: 408AN: 251288Hom.: 3 AF XY: 0.00127 AC XY: 172AN XY: 135820
GnomAD4 exome AF: 0.000603 AC: 881AN: 1461822Hom.: 12 Cov.: 31 AF XY: 0.000484 AC XY: 352AN XY: 727208
GnomAD4 genome AF: 0.00622 AC: 946AN: 152100Hom.: 13 Cov.: 30 AF XY: 0.00613 AC XY: 456AN XY: 74344
ClinVar
Submissions by phenotype
not provided Benign:4
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not specified Benign:2
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p.Tyr143Tyr in exon 5 of NLRP3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 2.26% (226/10022) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs56710146). -
Familial cold autoinflammatory syndrome 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
NLRP3-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Cryopyrin associated periodic syndrome Benign:1
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Autoinflammatory syndrome Benign:1
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Familial amyloid nephropathy with urticaria AND deafness Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Chronic infantile neurological, cutaneous and articular syndrome Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at