rs703468

Variant names:

• chr19-54974418-G-A
• rs703468
• NM_017852.5:c.281-82G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54974418-G-A
• chr19-54974418-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017852.5(NLRP2):​c.281-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 975,416 control chromosomes in the GnomAD database, including 25,965 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 0.23 (4060 hom., cov: 32)
  • Exomes 𝑓: 0.22 (21905 hom.)
• Consequence: NLRP2 NM_017852.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 4 publications found

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]

RPL36AP50 (HGNC:36372): (ribosomal protein L36a pseudogene 50)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP2	NM_017852.5	c.281-82G>A		intron_variant	Intron 2 of 12	ENST00000448584.7	NP_060322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP2	ENST00000448584.7	c.281-82G>A		intron_variant	Intron 2 of 12	1	NM_017852.5	ENSP00000409370.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34450 AN: 151890 Hom.: 4065 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.224 AC: 184507 AN: 823410 Hom.: 21905 Cov.: 12 AF XY: 0.223 AC XY: 97125 AN XY: 435622

African (AFR) AF: 0.240 AC: 5067 AN: 21128

American (AMR) AF: 0.247 AC: 10649 AN: 43102

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 4588 AN: 22096

East Asian (EAS) AF: 0.399 AC: 14695 AN: 36792

South Asian (SAS) AF: 0.201 AC: 14682 AN: 73006

European-Finnish (FIN) AF: 0.184 AC: 9646 AN: 52320

Middle Eastern (MID) AF: 0.246 AC: 975 AN: 3962

European-Non Finnish (NFE) AF: 0.217 AC: 115568 AN: 531750

Other (OTH) AF: 0.220 AC: 8637 AN: 39254

GnomAD4 genome AF: 0.227 AC: 34457 AN: 152006 Hom.: 4060 Cov.: 32 AF XY: 0.225 AC XY: 16711 AN XY: 74330

African (AFR) AF: 0.236 AC: 9810 AN: 41492

American (AMR) AF: 0.220 AC: 3359 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1959 AN: 5162

South Asian (SAS) AF: 0.205 AC: 985 AN: 4816

European-Finnish (FIN) AF: 0.173 AC: 1832 AN: 10582

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15082 AN: 67934

Other (OTH) AF: 0.222 AC: 467 AN: 2108

Alfa AF: 0.234 Hom.: 1277

Bravo AF: 0.232

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		1.0
PromoterAI		-0.0078	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs703468; hg19: chr19-55485786; COSMIC: COSV54759354; COSMIC: COSV54759354;