19-55808834-C-T

Variant summary

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

The NM_001394894.2(NLRP11):c.1776G>A(p.Arg592=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,613,472 control chromosomes in the GnomAD database, including 5,257 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 0.10 (1042 hom., cov: 32)
  • Exomes 𝑓: 0.058 (4215 hom.)
• Consequence: NLRP11 NM_001394894.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP11	NM_001394894.2	c.1776G>A	p.Arg592=	synonymous_variant	3/10	ENST00000589093.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP11	ENST00000589093.6	c.1776G>A	p.Arg592=	synonymous_variant	3/10	1	NM_001394894.2	P1

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15184 AN: 152060 Hom.: 1041 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0927

GnomAD3 exomes AF: 0.0989 AC: 24839 AN: 251190 Hom.: 1940 AF XY: 0.0887 AC XY: 12041 AN XY: 135750

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.223

Gnomad SAS exome AF: 0.0461

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.0460

Gnomad OTH exome AF: 0.0866

GnomAD4 exome AF: 0.0580 AC: 84706 AN: 1461294 Hom.: 4215 Cov.: 32 AF XY: 0.0566 AC XY: 41119 AN XY: 726988

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.0470

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0397

Gnomad4 OTH exome AF: 0.0723

GnomAD4 genome AF: 0.0999 AC: 15198 AN: 152178 Hom.: 1042 Cov.: 32 AF XY: 0.105 AC XY: 7840 AN XY: 74400

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0575 Hom.: 512

Bravo AF: 0.107

Asia WGS AF: 0.134 AC: 465 AN: 3478

EpiCase AF: 0.0448

EpiControl AF: 0.0476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.0
Dann	Benign	0.46

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: rs16986626; hg19: chr19-56320200; COSMIC: COSV64086257; COSMIC: COSV64086257;