NM_001394894.2:c.-63+2730T>A

Variant names:

• chr19-55829233-A-T
• rs2616944
• NM_001394894.2:c.-63+2730T>A

Variant summary

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

The NM_001394894.2(NLRP11):​c.-63+2730T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 151,696 control chromosomes in the GnomAD database, including 850 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 0.087 (850 hom., cov: 30)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 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.-63+2730T>A		intron	N/A	NP_001381823.1
	NLRP11	NM_145007.5		c.-63+2730T>A		intron	N/A	NP_659444.2
	NLRP11	NM_001385451.2		c.-63+2730T>A		intron	N/A	NP_001372380.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.-63+2730T>A		intron	N/A	ENSP00000466285.1
	NLRP11	ENST00000592953.5	TSL:1	c.-27+2730T>A		intron	N/A	ENSP00000468196.1
	NLRP11	ENST00000590409.5	TSL:1	n.-27+2730T>A		intron	N/A	ENSP00000466582.1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13204 AN: 151578 Hom.: 846 Cov.: 30

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0878

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

GnomAD4 genome AF: 0.0872 AC: 13225 AN: 151696 Hom.: 850 Cov.: 30 AF XY: 0.0874 AC XY: 6480 AN XY: 74112

African (AFR) AF: 0.150 AC: 6196 AN: 41260

American (AMR) AF: 0.128 AC: 1948 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5174

South Asian (SAS) AF: 0.0357 AC: 172 AN: 4818

European-Finnish (FIN) AF: 0.0344 AC: 361 AN: 10480

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0405 AC: 2751 AN: 67944

Other (OTH) AF: 0.0874 AC: 184 AN: 2106

Alfa AF: 0.0573 Hom.: 49

Bravo AF: 0.0981

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		1.2
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: rs2616944; hg19: chr19-56340599;