chr19-55802162-G-A

Variant names:

• chr19-55802162-G-A
• rs299175
• NM_001394894.2:c.2004-423C>T

Variant summary

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

The NM_001394894.2(NLRP11):​c.2004-423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,934 control chromosomes in the GnomAD database, including 13,943 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 0.43 (13943 hom., cov: 32)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	NM_001394894.2	MANE Select	c.2004-423C>T		intron	N/A	NP_001381823.1	P59045-1
	NLRP11	NM_145007.5		c.2004-423C>T		intron	N/A	NP_659444.2	P59045-1
	NLRP11	NM_001385451.2		c.1842-423C>T		intron	N/A	NP_001372380.1	P59045-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.2004-423C>T		intron	N/A	ENSP00000466285.1	P59045-1
	NLRP11	ENST00000592953.5	TSL:1	c.1707-423C>T		intron	N/A	ENSP00000468196.1	P59045-3
	NLRP11	ENST00000590409.5	TSL:1	n.1707-423C>T		intron	N/A	ENSP00000466582.1	K7EMN8

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64909 AN: 151814 Hom.: 13925 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.428 AC: 64975 AN: 151934 Hom.: 13943 Cov.: 32 AF XY: 0.426 AC XY: 31623 AN XY: 74246

African (AFR) AF: 0.381 AC: 15770 AN: 41418

American (AMR) AF: 0.453 AC: 6912 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1974 AN: 5166

South Asian (SAS) AF: 0.377 AC: 1815 AN: 4820

European-Finnish (FIN) AF: 0.445 AC: 4680 AN: 10528

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30909 AN: 67972

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.444 Hom.: 55025

Bravo AF: 0.431

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.75
PhyloP100		0.36
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: rs299175; hg19: chr19-56313528;