rs140769141
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_144687.4(NLRP12):c.3024C>T(p.Asn1008=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,614,136 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 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00066 ( 0 hom. )
Consequence
NLRP12
NM_144687.4 synonymous
NM_144687.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.694
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 19-53795933-G-A is Benign according to our data. Variant chr19-53795933-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 330002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53795933-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.694 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00127 (194/152282) while in subpopulation AFR AF= 0.00334 (139/41568). AF 95% confidence interval is 0.00289. There are 0 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 194 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP12 | NM_144687.4 | c.3024C>T | p.Asn1008= | synonymous_variant | 9/10 | ENST00000324134.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.3024C>T | p.Asn1008= | synonymous_variant | 9/10 | 1 | NM_144687.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00127 AC: 194AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000509 AC: 128AN: 251432Hom.: 0 AF XY: 0.000508 AC XY: 69AN XY: 135900
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GnomAD4 exome AF: 0.000664 AC: 971AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.000633 AC XY: 460AN XY: 727222
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GnomAD4 genome ? AF: 0.00127 AC: 194AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
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 | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 02, 2020 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | NLRP12: BP4, BP7 - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 02, 2020 | - - |
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