rs1363758

Positions:

• chr19-55818381-G-T

Variant summary

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

The NM_001394894.2(NLRP11):​c.-62-145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 555,404 control chromosomes in the GnomAD database, including 3,073 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 0.081 (642 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2431 hom.)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

Genes affected

NLRP11 (HGNC:22945): (NLR family pyrin domain containing 11) This gene is a member of the the NOD-like receptor protein (NLRP) gene family and encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain and a C-terminal leucine-rich repeats (LRR) region. This gene has been shown to regulate caspases in the proinflammatory signal transduction pathway and, based on studies of other members of the NLRP gene family with similar domain structure, is predicted to form part of the multiprotein inflammasome complex. Alternative splicing produces multiple transcript variants encoding distince isoforms. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP11	NM_001394894.2	c.-62-145C>A		intron_variant		ENST00000589093.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP11	ENST00000589093.6	c.-62-145C>A		intron_variant		1	NM_001394894.2	P1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12382 AN: 152112 Hom.: 642 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.103 AC: 41372 AN: 403174 Hom.: 2431 AF XY: 0.100 AC XY: 21183 AN XY: 210894

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.0671

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0779

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0862

GnomAD4 genome AF: 0.0813 AC: 12380 AN: 152230 Hom.: 642 Cov.: 32 AF XY: 0.0834 AC XY: 6209 AN XY: 74422

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0970 Hom.: 1044

Bravo AF: 0.0702

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1363758; hg19: chr19-56329747;