rs368633277
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_144687.4(NLRP12):c.2748G>A(p.Gln916=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,613,886 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 (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
NLRP12
NM_144687.4 synonymous
NM_144687.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.247
Genes affected
NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 19-53801235-C-T is Benign according to our data. Variant chr19-53801235-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 330013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.247 with no splicing effect.
BS2
?
High AC in GnomAd at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP12 | NM_144687.4 | c.2748G>A | p.Gln916= | synonymous_variant | 7/10 | ENST00000324134.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.2748G>A | p.Gln916= | synonymous_variant | 7/10 | 1 | NM_144687.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000132 AC: 20AN: 151916Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000124 AC: 31AN: 250684Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135576
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GnomAD4 exome AF: 0.000229 AC: 335AN: 1461856Hom.: 0 Cov.: 35 AF XY: 0.000212 AC XY: 154AN XY: 727228
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GnomAD4 genome ? AF: 0.000132 AC: 20AN: 152030Hom.: 0 Cov.: 30 AF XY: 0.000135 AC XY: 10AN XY: 74288
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
NLRP12-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 01, 2024 | 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). - |
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