Variant 11-7038594-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_176822.4(NLRP14):c.8A>G(p.Asp3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,648 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0056 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 5 hom. )

Consequence

NLRP14
NM_176822.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.922

Variant links:

Genes affected

NLRP14 (HGNC:22939): (NLR family pyrin domain containing 14) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]

NLRP14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044326186).

BP6

Variant 11-7038594-A-G is Benign according to our data. Variant chr11-7038594-A-G is described in ClinVar as [Benign]. Clinvar id is 3053270.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00559 (851/152236) while in subpopulation AFR AF= 0.0198 (824/41522). AF 95% confidence interval is 0.0187. There are 5 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NLRP14	NM_176822.4 linkuse as main transcript	c.8A>G	p.Asp3Gly	missense_variant	2/12	ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2 linkuse as main transcript	c.8A>G	p.Asp3Gly	missense_variant	2/11		XP_011518346.1
NLRP14	XM_047426867.1 linkuse as main transcript	c.8A>G	p.Asp3Gly	missense_variant	2/11		XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5 linkuse as main transcript	c.8A>G	p.Asp3Gly	missense_variant	2/12	5	NM_176822.4	ENSP00000299481	P1

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

849

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00154

AC:

386

AN:

251040

Hom.:

AF XY:

0.00128

AC XY:

174

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000541

AC:

791

AN:

1461412

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

340

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00559

AC:

851

AN:

152236

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

399

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000930

Hom.:

Bravo

AF:

0.00648

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00200

AC:

243

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NLRP14-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.080

Sift

Pathogenic

0.0

Sift4G

Benign

0.12

Polyphen

0.13

Vest4

0.41

MVP

0.61

MPC

0.15

ClinPred

0.086

GERP RS

0.42

Varity_R

0.21

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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