19-55808834-C-T

Variant names:

• chr19-55808834-C-T
• rs16986626
• NM_001394894.2:c.1776G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001394894.2(NLRP11):​c.1776G>A​(p.Arg592Arg) 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
• Publications: 10 publications found

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]

NLRP11 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394894.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	NM_001394894.2	MANE Select	c.1776G>A	p.Arg592Arg	synonymous	Exon 3 of 10	NP_001381823.1
	NLRP11	NM_145007.5		c.1776G>A	p.Arg592Arg	synonymous	Exon 5 of 12	NP_659444.2
	NLRP11	NM_001385451.2		c.1776G>A	p.Arg592Arg	synonymous	Exon 5 of 11	NP_001372380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.1776G>A	p.Arg592Arg	synonymous	Exon 3 of 10	ENSP00000466285.1
	NLRP11	ENST00000592953.5	TSL:1	c.1479G>A	p.Arg493Arg	synonymous	Exon 2 of 9	ENSP00000468196.1
	NLRP11	ENST00000590409.5	TSL:1	n.1479G>A		non_coding_transcript_exon	Exon 4 of 12	ENSP00000466582.1

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

GnomAD2 exomes AF: 0.0989 AC: 24839 AN: 251190 AF XY: 0.0887

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 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

African (AFR) AF: 0.161 AC: 5388 AN: 33470

American (AMR) AF: 0.206 AC: 9228 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2807 AN: 26132

East Asian (EAS) AF: 0.208 AC: 8265 AN: 39692

South Asian (SAS) AF: 0.0470 AC: 4051 AN: 86240

European-Finnish (FIN) AF: 0.111 AC: 5947 AN: 53416

Middle Eastern (MID) AF: 0.0818 AC: 472 AN: 5768

European-Non Finnish (NFE) AF: 0.0397 AC: 44181 AN: 1111482

Other (OTH) AF: 0.0723 AC: 4367 AN: 60378

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

African (AFR) AF: 0.158 AC: 6555 AN: 41496

American (AMR) AF: 0.149 AC: 2278 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1168 AN: 5180

South Asian (SAS) AF: 0.0491 AC: 237 AN: 4826

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3007 AN: 68020

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0673 Hom.: 1014

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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