rs10500321

Variant names:

• chr19-55808205-A-G
• rs10500321
• NM_001394894.2:c.1842-191T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55808205-A-G
• chr19-55808205-A-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.1842-191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,246 control chromosomes in the GnomAD database, including 2,091 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 (2091 hom., cov: 33)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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.1842-191T>C		intron	N/A	NP_001381823.1	P59045-1
	NLRP11	NM_145007.5		c.1842-191T>C		intron	N/A	NP_659444.2	P59045-1
	NLRP11	NM_001385451.2		c.1841+564T>C		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.1842-191T>C		intron	N/A	ENSP00000466285.1	P59045-1
	NLRP11	ENST00000592953.5	TSL:1	c.1545-191T>C		intron	N/A	ENSP00000468196.1	P59045-3
	NLRP11	ENST00000590409.5	TSL:1	n.1545-191T>C		intron	N/A	ENSP00000466582.1	K7EMN8

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22649 AN: 152128 Hom.: 2086 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.149 AC: 22668 AN: 152246 Hom.: 2091 Cov.: 33 AF XY: 0.144 AC XY: 10684 AN XY: 74446

African (AFR) AF: 0.260 AC: 10780 AN: 41504

American (AMR) AF: 0.156 AC: 2390 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3470

East Asian (EAS) AF: 0.178 AC: 925 AN: 5184

South Asian (SAS) AF: 0.0503 AC: 243 AN: 4830

European-Finnish (FIN) AF: 0.0402 AC: 427 AN: 10628

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6981 AN: 68012

Other (OTH) AF: 0.135 AC: 286 AN: 2112

Alfa AF: 0.0771 Hom.: 151

Bravo AF: 0.163

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.77
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10500321;

hg19: chr19-56319571;