11-7038750-G-A

Position:

chr11-7038750-G-A

Variant summary

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

The NM_176822.4(NLRP14):c.164G>A(p.Arg55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,480 control chromosomes in the GnomAD database, including 31,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.15 ( 2153 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29778 hom. )

Consequence

NLRP14
NM_176822.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.358

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010732114).

BP6

Variant 11-7038750-G-A is Benign according to our data. Variant chr11-7038750-G-A is described in ClinVar as [Benign]. Clinvar id is 1245032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NLRP14	NM_176822.4 linkuse as main transcript	c.164G>A	p.Arg55Gln	missense_variant	2/12	ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2 linkuse as main transcript	c.164G>A	p.Arg55Gln	missense_variant	2/11		XP_011518346.1
NLRP14	XM_047426867.1 linkuse as main transcript	c.164G>A	p.Arg55Gln	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.164G>A	p.Arg55Gln	missense_variant	2/12	5	NM_176822.4	ENSP00000299481	P1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23020

AN:

152088

Hom.:

2153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0813

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.0854

Gnomad FIN

AF:

0.0970

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.148

AC:

37151

AN:

250728

Hom.:

3323

AF XY:

0.151

AC XY:

20457

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.0151

Gnomad SAS exome

AF:

0.0905

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.194

AC:

284024

AN:

1461274

Hom.:

29778

Cov.:

AF XY:

0.193

AC XY:

140056

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0781

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.0189

Gnomad4 SAS exome

AF:

0.0987

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.151

AC:

23026

AN:

152206

Hom.:

2153

Cov.:

AF XY:

0.145

AC XY:

10770

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0814

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.0859

Gnomad4 FIN

AF:

0.0970

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.191

Hom.:

4702

Bravo

AF:

0.154

TwinsUK

AF:

0.218

AC:

810

ALSPAC

AF:

0.218

AC:

840

ESP6500AA

AF:

0.0841

AC:

370

ESP6500EA

AF:

0.214

AC:

1840

ExAC

AF:

0.149

AC:

18152

Asia WGS

AF:

0.0550

AC:

193

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.226

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	clinical testing	GeneDx	Jun 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

NLRP14-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

0.16

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

REVEL

Benign

0.21

Sift

Benign

0.39

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.30

MPC

0.15

ClinPred

0.077

GERP RS

2.2

Varity_R

0.33

gMVP

0.25

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