Variant 19-55857719-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_134444.5(NLRP4):c.326G>A(p.Arg109His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,613,496 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 7 hom. )

Consequence

NLRP4
NM_134444.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.16

Variant links:

Genes affected

NLRP4 (HGNC:22943): (NLR family pyrin domain containing 4) The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autophagy and type I interferon signaling pathways as a result of protein interactions with its NACHT domain. The PYD domain has also been shown to be important in the inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells). [provided by RefSeq, Dec 2016]

NLRP4 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=0.004376352).

BP6

Variant 19-55857719-G-A is Benign according to our data. Variant chr19-55857719-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650543.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NLRP4	NM_134444.5 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	3/10	ENST00000301295.11	NP_604393.2
NLRP4	XM_017026344.1 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	2/8		XP_016881833.1
NLRP4	XM_017026345.1 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	2/8		XP_016881834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NLRP4	ENST00000301295.11 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	3/10	1	NM_134444.5	ENSP00000301295.4	Q96MN2-1
NLRP4	ENST00000587891.5 linkuse as main transcript	c.101G>A	p.Arg34His	missense_variant	1/8	2		ENSP00000465463.1	Q96MN2-3
NLRP4	ENST00000587464.1 linkuse as main transcript	c.326G>A	p.Arg109His	missense_variant	3/3	2		ENSP00000468496.1	K7ES09

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000677

AC:

170

AN:

251288

Hom.:

AF XY:

0.000780

AC XY:

106

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000452

AC:

661

AN:

1461208

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00356

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000262

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000341

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000354

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000700

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000119

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

Mar 01, 2023

NLRP4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.043

DANN

Benign

0.38

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00046

LIST_S2

Benign

0.29

T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

1.4

N;.;.

REVEL

Benign

0.081

Sift

Benign

0.79

T;.;.

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.034

MVP

0.36

MPC

0.050

ClinPred

0.0031

GERP RS

-6.6

Varity_R

0.017

gMVP

0.044

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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