rs12461110

Variant names:

• chr19-55809297-G-A
• rs12461110
• NM_001394894.2:c.1313C>T

Variant summary

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

The NM_145007.5(NLRP11):​c.1313C>T​(p.Pro438Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,613,138 control chromosomes in the GnomAD database, including 94,623 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6490 hom., cov: 32)
  • Exomes 𝑓: 0.34 (88133 hom.)
• Consequence: NLRP11 NM_145007.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 48 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 (MetaRNN=0.0031175911).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145007.5. 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.1313C>T	p.Pro438Leu	missense	Exon 3 of 10	NP_001381823.1
	NLRP11	NM_145007.5		c.1313C>T	p.Pro438Leu	missense	Exon 5 of 12	NP_659444.2
	NLRP11	NM_001385451.2		c.1313C>T	p.Pro438Leu	missense	Exon 5 of 11	NP_001372380.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.1313C>T	p.Pro438Leu	missense	Exon 3 of 10	ENSP00000466285.1
	NLRP11	ENST00000592953.5	TSL:1	c.1016C>T	p.Pro339Leu	missense	Exon 2 of 9	ENSP00000468196.1
	NLRP11	ENST00000590409.5	TSL:1	n.1016C>T		non_coding_transcript_exon	Exon 4 of 12	ENSP00000466582.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40631 AN: 151790 Hom.: 6490 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.321 AC: 80523 AN: 251080 AF XY: 0.323

Gnomad AFR exome AF: 0.0686

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.305

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.343 AC: 500856 AN: 1461228 Hom.: 88133 Cov.: 38 AF XY: 0.342 AC XY: 248540 AN XY: 726888

African (AFR) AF: 0.0632 AC: 2115 AN: 33474

American (AMR) AF: 0.376 AC: 16806 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7065 AN: 26134

East Asian (EAS) AF: 0.271 AC: 10766 AN: 39682

South Asian (SAS) AF: 0.298 AC: 25724 AN: 86248

European-Finnish (FIN) AF: 0.311 AC: 16579 AN: 53382

Middle Eastern (MID) AF: 0.233 AC: 1342 AN: 5766

European-Non Finnish (NFE) AF: 0.361 AC: 400997 AN: 1111450

Other (OTH) AF: 0.322 AC: 19462 AN: 60382

GnomAD4 genome AF: 0.268 AC: 40640 AN: 151910 Hom.: 6490 Cov.: 32 AF XY: 0.267 AC XY: 19832 AN XY: 74252

African (AFR) AF: 0.0785 AC: 3255 AN: 41450

American (AMR) AF: 0.349 AC: 5333 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1557 AN: 5172

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4810

European-Finnish (FIN) AF: 0.302 AC: 3165 AN: 10496

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23926 AN: 67946

Other (OTH) AF: 0.283 AC: 595 AN: 2104

Alfa AF: 0.321 Hom.: 32706

Bravo AF: 0.264

TwinsUK AF: 0.368 AC: 1364

ALSPAC AF: 0.358 AC: 1379

ESP6500AA AF: 0.0828 AC: 365

ESP6500EA AF: 0.343 AC: 2954

ExAC AF: 0.316 AC: 38321

Asia WGS AF: 0.268 AC: 931 AN: 3478

EpiCase AF: 0.344

EpiControl AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.40
DANN	Benign	0.87
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.2
PrimateAI	Benign	0.22	T
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.068
ClinPred		0.0078	T
GERP RS		-4.4
Varity_R		0.029
gMVP		0.50
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: rs12461110; hg19: chr19-56320663; COSMIC: COSV64086315; COSMIC: COSV64086315;