Variant 19-55000769-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017852.5(NLRP2):c.3060C>A(p.Ile1020Ile) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Variant links:

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]

NLRP2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
NLRP2	NM_017852.5 link	c.3060C>A	p.Ile1020Ile	synonymous_variant	13/13	ENST00000448584.7	NP_060322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP2	ENST00000448584.7 link	c.3060C>A	p.Ile1020Ile	synonymous_variant	13/13	1	NM_017852.5	ENSP00000409370.2		Q9NX02-1

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

79836

AN:

151518

Hom.:

21622

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.524

AC XY:

380284

AN XY:

725704

show subpopulations

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.:

AF XY:

0.528

AC XY:

39131

AN XY:

74060

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over