Variant 19-55947936-A-C 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_176811.2(NLRP8):c.34A>C(p.Ile12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,613,690 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 29 hom. )

Consequence

NLRP8
NM_176811.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.84

Variant links:

Genes affected

NLRP8 (HGNC:22940): (NLR family pyrin domain containing 8) This gene encodes a member of the nucleotide-binding oligomerization domain/ leucine rich repeat/ pyrin domain containing (NLRP) subfamily, which belongs to the Nod-like receptor family of proteins. NLRP genes play roles in the mammalian innate immune system through inflammasome formation and activation of caspases. In addition, NLRP genes have been found to function during mammalian reproduction. Consistent with a function during human preimplantation development, this gene is expressed at high levels in oocytes with decreased levels in embryos. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

NLRP8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007263452).

BP6

Variant 19-55947936-A-C is Benign according to our data. Variant chr19-55947936-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP8	NM_176811.2 linkuse as main transcript	c.34A>C	p.Ile12Leu	missense_variant	1/10	ENST00000291971.7	NP_789781.2	Q86W28-1
NLRP8	NM_001317000.1 linkuse as main transcript	c.34A>C	p.Ile12Leu	missense_variant	1/10		NP_001303929.1	Q86W28-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP8	ENST00000291971.7 linkuse as main transcript	c.34A>C	p.Ile12Leu	missense_variant	1/10	1	NM_176811.2	ENSP00000291971.3		Q86W28-1
NLRP8	ENST00000590542.1 linkuse as main transcript	c.34A>C	p.Ile12Leu	missense_variant	1/10	1		ENSP00000468121.1		Q86W28-2

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

432

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000991

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00279

AC:

701

AN:

251224

Hom.:

AF XY:

0.00288

AC XY:

391

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000984

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00502

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00508

AC:

7427

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00498

AC XY:

3618

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.00623

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00284

AC:

432

AN:

152096

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000988

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00442

Hom.:

Bravo

AF:

0.00287

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00294

AC:

357

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00379

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

NLRP8: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.0080

DANN

Benign

0.64

DEOGEN2

Benign

0.00096

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

N;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.52

T;T

Polyphen

0.0010

B;B

Vest4

0.10

MVP

0.25

MPC

0.068

ClinPred

0.0094

GERP RS

-1.7

Varity_R

0.098

gMVP

0.018

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