rs16986669

Variant names:

• chr19-55828828-C-T
• rs16986669
• NM_001394894.2:c.-63+3135G>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+3135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 152,114 control chromosomes in the GnomAD database, including 871 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 0.088 (871 hom., cov: 32)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP11	NM_001394894.2	c.-63+3135G>A		intron_variant	Intron 1 of 9	ENST00000589093.6	NP_001381823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP11	ENST00000589093.6	c.-63+3135G>A		intron_variant	Intron 1 of 9	1	NM_001394894.2	ENSP00000466285.1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13295 AN: 151996 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0875 AC: 13314 AN: 152114 Hom.: 871 Cov.: 32 AF XY: 0.0877 AC XY: 6519 AN XY: 74348

African (AFR) AF: 0.151 AC: 6274 AN: 41496

American (AMR) AF: 0.128 AC: 1959 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3466

East Asian (EAS) AF: 0.233 AC: 1205 AN: 5174

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4812

European-Finnish (FIN) AF: 0.0344 AC: 364 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0406 AC: 2757 AN: 67990

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0676 Hom.: 75

Bravo AF: 0.0985

Asia WGS AF: 0.108 AC: 375 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	2.8
DANN	Benign	0.66
PhyloP100		-1.7
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: rs16986669; hg19: chr19-56340194;