rs61741347
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000324134.11(NLRP12):āc.2754G>Cā(p.Leu918=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,836 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L918L) has been classified as Likely benign.
Frequency
Consequence
ENST00000324134.11 splice_region, 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NLRP12 | NM_144687.4 | c.2754G>C | p.Leu918= | splice_region_variant, synonymous_variant | 7/10 | ENST00000324134.11 | NP_653288.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.2754G>C | p.Leu918= | splice_region_variant, synonymous_variant | 7/10 | 1 | NM_144687.4 | ENSP00000319377 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00638 AC: 969AN: 151880Hom.: 11 Cov.: 30
GnomAD3 exomes AF: 0.00163 AC: 407AN: 250372Hom.: 5 AF XY: 0.00121 AC XY: 164AN XY: 135452
GnomAD4 exome AF: 0.000662 AC: 968AN: 1461840Hom.: 14 Cov.: 35 AF XY: 0.000586 AC XY: 426AN XY: 727216
GnomAD4 genome AF: 0.00642 AC: 976AN: 151996Hom.: 11 Cov.: 30 AF XY: 0.00617 AC XY: 458AN XY: 74272
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
NLRP12-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2019 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at