19-55818381-G-T

Variant names:

• chr19-55818381-G-T
• rs1363758
• NM_001394894.2:c.-62-145C>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.-62-145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 555,404 control chromosomes in the GnomAD database, including 3,073 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 0.081 (642 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2431 hom.)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 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.-62-145C>A		intron	N/A	NP_001381823.1
	NLRP11	NM_145007.5		c.-62-145C>A		intron	N/A	NP_659444.2
	NLRP11	NM_001385451.2		c.-62-145C>A		intron	N/A	NP_001372380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.-62-145C>A		intron	N/A	ENSP00000466285.1
	NLRP11	ENST00000592953.5	TSL:1	c.-26-8043C>A		intron	N/A	ENSP00000468196.1
	NLRP11	ENST00000590409.5	TSL:1	n.-26-8043C>A		intron	N/A	ENSP00000466582.1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12382 AN: 152112 Hom.: 642 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.103 AC: 41372 AN: 403174 Hom.: 2431 AF XY: 0.100 AC XY: 21183 AN XY: 210894

African (AFR) AF: 0.0225 AC: 260 AN: 11576

American (AMR) AF: 0.0414 AC: 626 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 855 AN: 12738

East Asian (EAS) AF: 0.145 AC: 4097 AN: 28332

South Asian (SAS) AF: 0.0779 AC: 2873 AN: 36860

European-Finnish (FIN) AF: 0.144 AC: 3813 AN: 26528

Middle Eastern (MID) AF: 0.0524 AC: 93 AN: 1774

European-Non Finnish (NFE) AF: 0.108 AC: 26708 AN: 246496

Other (OTH) AF: 0.0862 AC: 2047 AN: 23758

GnomAD4 genome AF: 0.0813 AC: 12380 AN: 152230 Hom.: 642 Cov.: 32 AF XY: 0.0834 AC XY: 6209 AN XY: 74422

African (AFR) AF: 0.0241 AC: 1003 AN: 41540

American (AMR) AF: 0.0427 AC: 653 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3470

East Asian (EAS) AF: 0.133 AC: 688 AN: 5182

South Asian (SAS) AF: 0.0971 AC: 468 AN: 4820

European-Finnish (FIN) AF: 0.155 AC: 1645 AN: 10582

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7383 AN: 68020

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0962 Hom.: 2347

Bravo AF: 0.0702

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		-0.34
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1363758; hg19: chr19-56329747;