Variant rs12461110 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394894.2(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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6490 hom., cov: 32)

Exomes 𝑓: 0.34 ( 88133 hom. )

Consequence

NLRP11
NM_001394894.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP11	NM_001394894.2 linkuse as main transcript	c.1313C>T	p.Pro438Leu	missense_variant	3/10	ENST00000589093.6	NP_001381823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP11	ENST00000589093.6 linkuse as main transcript	c.1313C>T	p.Pro438Leu	missense_variant	3/10	1	NM_001394894.2	ENSP00000466285	P1	P59045-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40631

AN:

151790

Hom.:

6490

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.321

AC:

80523

AN:

251080

Hom.:

13618

AF XY:

0.323

AC XY:

43819

AN XY:

135726

show subpopulations

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 SAS exome

AF:

0.300

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.:

AF XY:

0.342

AC XY:

248540

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.268

AC:

40640

AN:

151910

Hom.:

6490

Cov.:

AF XY:

0.267

AC XY:

19832

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0785

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.352

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.329

Hom.:

15962

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.65

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

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;L

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.22

Sift4G

Benign

0.13

T;T;T

Polyphen

0.99

D;.;P

Vest4

0.068

ClinPred

0.0078

GERP RS

-4.4

Varity_R

0.029

gMVP

0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over