1-247424106-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001243133.2(NLRP3):c.657C>T(p.Thr219Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 1,613,902 control chromosomes in the GnomAD database, including 5,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T219T) has been classified as Likely 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.657C>T | p.Thr219Thr | 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.657C>T | p.Thr219Thr | synonymous_variant | Exon 4 of 10 | 1 | NM_001243133.2 | ENSP00000337383.4 |
Frequencies
GnomAD3 genomes AF: 0.110 AC: 16651AN: 151920Hom.: 1290 Cov.: 31
GnomAD3 exomes AF: 0.0802 AC: 20156AN: 251268Hom.: 1098 AF XY: 0.0755 AC XY: 10254AN XY: 135788
GnomAD4 exome AF: 0.0647 AC: 94567AN: 1461864Hom.: 3886 Cov.: 32 AF XY: 0.0639 AC XY: 46440AN XY: 727232
GnomAD4 genome AF: 0.110 AC: 16670AN: 152038Hom.: 1291 Cov.: 31 AF XY: 0.111 AC XY: 8252AN XY: 74338
ClinVar
Submissions by phenotype
not specified Benign:4
p.Thr221Thr in exon 5 of the NLPR3 gene: This variant is not expected to have cl inical significance because it does not alter an amino acid residue and it has b een identified in 8% (23018/276946) of the total chromosomes by the the Genome A ggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs7525979). -
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not provided Benign:3
This variant is associated with the following publications: (PMID: 30246732, 30131971) -
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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. -
Cryopyrin associated periodic 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