Variant 11-7038861-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_176822.4(NLRP14):c.275A>G(p.Lys92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,613,208 control chromosomes in the GnomAD database, including 2,777 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.039 ( 227 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2550 hom. )

Consequence

NLRP14
NM_176822.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0630

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013730526).

BP6

Variant 11-7038861-A-G is Benign according to our data. Variant chr11-7038861-A-G is described in ClinVar as [Benign]. Clinvar id is 1241370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP14	NM_176822.4 linkuse as main transcript	c.275A>G	p.Lys92Arg	missense_variant	2/12	ENST00000299481.5	NP_789792.1	Q86W24
NLRP14	XM_011520044.2 linkuse as main transcript	c.275A>G	p.Lys92Arg	missense_variant	2/11		XP_011518346.1
NLRP14	XM_047426867.1 linkuse as main transcript	c.275A>G	p.Lys92Arg	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.275A>G	p.Lys92Arg	missense_variant	2/12	5	NM_176822.4	ENSP00000299481.5		Q86W24

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5923

AN:

152134

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0599

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0331

Gnomad OTH

AF:

0.0478

GnomAD3 exomes

AF:

0.0659

AC:

16425

AN:

249356

Hom.:

964

AF XY:

0.0667

AC XY:

9000

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.00773

Gnomad AMR exome

AF:

0.0937

Gnomad ASJ exome

AF:

0.0267

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0544

Gnomad NFE exome

AF:

0.0346

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0433

AC:

63211

AN:

1460956

Hom.:

2550

Cov.:

AF XY:

0.0454

AC XY:

33001

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.00729

Gnomad4 AMR exome

AF:

0.0895

Gnomad4 ASJ exome

AF:

0.0259

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0521

Gnomad4 NFE exome

AF:

0.0305

Gnomad4 OTH exome

AF:

0.0506

GnomAD4 genome

AF:

0.0389

AC:

5926

AN:

152252

Hom.:

227

Cov.:

AF XY:

0.0412

AC XY:

3068

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00936

Gnomad4 AMR

AF:

0.0600

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0528

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0482

Alfa

AF:

0.0328

Hom.:

Bravo

AF:

0.0376

TwinsUK

AF:

0.0294

AC:

109

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.00841

AC:

ESP6500EA

AF:

0.0329

AC:

283

ExAC

AF:

0.0634

AC:

7697

Asia WGS

AF:

0.156

AC:

542

AN:

3478

EpiCase

AF:

0.0336

EpiControl

AF:

0.0343

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

NLRP14-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 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

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.33

REVEL

Benign

0.021

Sift

Benign

0.88

Sift4G

Benign

0.11

Polyphen

0.16

Vest4

0.035

MPC

0.018

ClinPred

0.0026

GERP RS

1.7

Varity_R

0.11

gMVP

0.23

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