rs382958

Positions:

• chr19-55928072-G-A
• chr19-55928072-G-C

Variant summary

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

The NM_176810.2(NLRP13):​c.320-3037C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,936 control chromosomes in the GnomAD database, including 28,148 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 0.60 (28148 hom., cov: 31)
• Consequence: NLRP13 NM_176810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP13	NM_176810.2	c.320-3037C>T		intron_variant		ENST00000342929.4
NLRP13	NM_001321057.1	c.320-3037C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP13	ENST00000342929.4	c.320-3037C>T		intron_variant		1	NM_176810.2	P2
NLRP13	ENST00000588751.5	c.320-3037C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91811 AN: 151818 Hom.: 28130 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.605 AC: 91876 AN: 151936 Hom.: 28148 Cov.: 31 AF XY: 0.611 AC XY: 45399 AN XY: 74254

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.610

Alfa AF: 0.576 Hom.: 12596

Bravo AF: 0.606

Asia WGS AF: 0.743 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.21

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: rs382958; hg19: chr19-56439438;