rs302827

Positions:

• chr19-55898856-C-T

Variant summary

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

The NM_176810.2(NLRP13):​c.2871G>A​(p.Leu957Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,612,626 control chromosomes in the GnomAD database, including 63,269 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 0.25 (4944 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58325 hom.)
• Consequence: NLRP13 NM_176810.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=0.299 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.2871G>A	p.Leu957Leu	synonymous_variant	10/11	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.2871G>A	p.Leu957Leu	synonymous_variant	10/12		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.2871G>A	p.Leu957Leu	synonymous_variant	10/11	1	NM_176810.2	ENSP00000343891.3
NLRP13	ENST00000588751.5	c.2871G>A	p.Leu957Leu	synonymous_variant	10/12	5		ENSP00000467899.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37951 AN: 151982 Hom.: 4942 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.274 AC: 68628 AN: 250212 Hom.: 9905 AF XY: 0.276 AC XY: 37328 AN XY: 135220

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.411

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.280 AC: 408580 AN: 1460526 Hom.: 58325 Cov.: 34 AF XY: 0.280 AC XY: 203406 AN XY: 726572

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.250 AC: 37969 AN: 152100 Hom.: 4944 Cov.: 32 AF XY: 0.249 AC XY: 18504 AN XY: 74344

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.284

Alfa AF: 0.276 Hom.: 9657

Bravo AF: 0.253

Asia WGS AF: 0.344 AC: 1194 AN: 3478

EpiCase AF: 0.282

EpiControl AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs302827; hg19: chr19-56410222; COSMIC: COSV61621081;