Variant 19-55785653-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394894.2(NLRP11):c.3074C>T(p.Ser1025Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,613,840 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 70 hom. )

Consequence

NLRP11
NM_001394894.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074005127).

BP6

Variant 19-55785653-G-A is Benign according to our data. Variant chr19-55785653-G-A is described in ClinVar as [Benign]. Clinvar id is 789353.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP11	NM_001394894.2 linkuse as main transcript	c.3074C>T	p.Ser1025Leu	missense_variant	10/10	ENST00000589093.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP11	ENST00000589093.6 linkuse as main transcript	c.3074C>T	p.Ser1025Leu	missense_variant	10/10	1	NM_001394894.2	P1	P59045-1
NLRP11	ENST00000592953.5 linkuse as main transcript	c.2777C>T	p.Ser926Leu	missense_variant	9/9	1			P59045-3
NLRP11	ENST00000590409.5 linkuse as main transcript	c.*888C>T		3_prime_UTR_variant, NMD_transcript_variant	12/12	1
NLRP11	ENST00000589824.6 linkuse as main transcript	c.2912C>T	p.Ser971Leu	missense_variant	8/8	5			P59045-2

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00673

AC:

1690

AN:

251286

Hom.:

AF XY:

0.00705

AC XY:

957

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.00794

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00637

GnomAD4 exome

AF:

0.00865

AC:

12648

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00843

AC XY:

6131

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00637

Gnomad4 ASJ exome

AF:

0.00735

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00262

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00745

GnomAD4 genome

AF:

0.00692

AC:

1054

AN:

152280

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

465

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00707

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0103

AC:

ExAC

AF:

0.00676

AC:

821

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

Cadd

Benign

2.9

Dann

Benign

0.96

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-0.84

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.39

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;.;P

Vest4

0.10

MVP

0.70

ClinPred

0.0044

GERP RS

-1.5

Varity_R

0.049

gMVP

0.066

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over