rs12768

chr19-55000769-C-Achr19-55000769-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017852.5(NLRP2):c.3060C>A(p.Ile1020=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,610,080 control chromosomes in the GnomAD database, including 224,951 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (21657 hom., cov: 29)
  • Exomes 𝑓: 0.52 (203294 hom.)
• Consequence: NLRP2 NM_017852.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

NLRP2 (HGNC:22948): (NLR family pyrin domain containing 2) This gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). Members of this gene family are thought to be important regulators of immune responses. This gene product interacts with components of the IkB kinase (IKK) complex, and can regulate both caspase-1 and NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity. The pyrin domain is necessary and sufficient for suppression of NF-kB activity. An allelic variant (rs147585490) has been found that is incapable of blocking the transcriptional activity of NF-kB. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-1.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP2	NM_017852.5	c.3060C>A	p.Ile1020=	synonymous_variant	13/13	ENST00000448584.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP2	ENST00000448584.7	c.3060C>A	p.Ile1020=	synonymous_variant	13/13	1	NM_017852.5	P2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79836 AN: 151518 Hom.: 21622 Cov.: 29

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.558

GnomAD3 exomes AF: 0.565 AC: 141895 AN: 251324 Hom.: 41403 AF XY: 0.557 AC XY: 75674 AN XY: 135854

Gnomad AFR exome AF: 0.461

Gnomad AMR exome AF: 0.755

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.707

Gnomad SAS exome AF: 0.542

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.524 AC: 763702 AN: 1458444 Hom.: 203294 Cov.: 40 AF XY: 0.524 AC XY: 380284 AN XY: 725704

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.746

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.724

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.527 AC: 79922 AN: 151636 Hom.: 21657 Cov.: 29 AF XY: 0.528 AC XY: 39131 AN XY: 74060

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.560

Alfa AF: 0.523 Hom.: 28309

Bravo AF: 0.539

Asia WGS AF: 0.637 AC: 2218 AN: 3478

EpiCase AF: 0.529

EpiControl AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.090
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12768; hg19: chr19-55512137;