rs2117900

Positions:

• chr19-55908124-A-G
• chr19-55908124-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176810.2(NLRP13):​c.2283-168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,772 control chromosomes in the GnomAD database, including 12,163 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 0.39 (12163 hom., cov: 30)
• Consequence: NLRP13 NM_176810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

NLRP13 (HGNC:22937): (NLR family pyrin domain containing 13) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.2283-168T>C		intron_variant		ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.2283-168T>C		intron_variant			NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.2283-168T>C		intron_variant		1	NM_176810.2	ENSP00000343891	P2
NLRP13	ENST00000588751.5	c.2283-168T>C		intron_variant		5		ENSP00000467899	A2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59710 AN: 151654 Hom.: 12145 Cov.: 30

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59777 AN: 151772 Hom.: 12163 Cov.: 30 AF XY: 0.390 AC XY: 28915 AN XY: 74154

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.381

Alfa AF: 0.367 Hom.: 13850

Bravo AF: 0.402

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.74

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: rs2117900; hg19: chr19-56419490;