rs2059152

Variant names:

• chr19-55806822-T-C
• rs2059152
• NM_001394894.2:c.2003+1031A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394894.2(NLRP11):​c.2003+1031A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,130 control chromosomes in the GnomAD database, including 2,297 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 0.15 (2297 hom., cov: 31)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP11	NM_001394894.2	c.2003+1031A>G		intron_variant	Intron 4 of 9	ENST00000589093.6	NP_001381823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP11	ENST00000589093.6	c.2003+1031A>G		intron_variant	Intron 4 of 9	1	NM_001394894.2	ENSP00000466285.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23515 AN: 152012 Hom.: 2291 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.155 AC: 23540 AN: 152130 Hom.: 2297 Cov.: 31 AF XY: 0.149 AC XY: 11110 AN XY: 74396

African (AFR) AF: 0.274 AC: 11372 AN: 41482

American (AMR) AF: 0.165 AC: 2516 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3472

East Asian (EAS) AF: 0.176 AC: 907 AN: 5148

South Asian (SAS) AF: 0.0505 AC: 244 AN: 4828

European-Finnish (FIN) AF: 0.0399 AC: 423 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7173 AN: 67998

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.130 Hom.: 237

Bravo AF: 0.170

Asia WGS AF: 0.103 AC: 359 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	0.79
DANN	Benign	0.45
PhyloP100		-0.20
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: rs2059152; hg19: chr19-56318188;