rs17280682

Variant names:

Variant summary

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

The NM_176822.4(NLRP14):c.3028C>T(p.Leu1010Phe) 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 1,608,730 control chromosomes in the GnomAD database, including 31,805 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2148 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29657 hom. )

Consequence

NLRP14
NM_176822.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.99

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=0.0010507703).

BP6

Variant 11-7070338-C-T is Benign according to our data. Variant chr11-7070338-C-T is described in ClinVar as [Benign]. Clinvar id is 1222316.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 rank	MANE	Protein	UniProt
NLRP14	NM_176822.4 link	c.3028C>T	p.Leu1010Phe	missense_variant	Exon 11 of 12	ENST00000299481.5	NP_789792.1	Q86W24
NLRP14	XM_011520044.2 link	c.2857C>T	p.Leu953Phe	missense_variant	Exon 10 of 11		XP_011518346.1
NLRP14	XM_047426867.1 link	c.2857C>T	p.Leu953Phe	missense_variant	Exon 10 of 11		XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5 link	c.3028C>T	p.Leu1010Phe	missense_variant	Exon 11 of 12	5	NM_176822.4	ENSP00000299481.5		Q86W24

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23045

AN:

152006

Hom.:

2148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0810

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.0144

Gnomad SAS

AF:

0.0852

Gnomad FIN

AF:

0.0972

Gnomad MID

AF:

0.186

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.148

AC:

37184

AN:

251174

Hom.:

3336

AF XY:

0.151

AC XY:

20460

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.0772

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.0150

Gnomad SAS exome

AF:

0.0896

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.194

AC:

282213

AN:

1456606

Hom.:

29657

Cov.:

AF XY:

0.192

AC XY:

139294

AN XY:

725018

show subpopulations

Gnomad4 AFR exome

AF:

0.0773

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.0188

Gnomad4 SAS exome

AF:

0.0976

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.152

AC:

23049

AN:

152124

Hom.:

2148

Cov.:

AF XY:

0.145

AC XY:

10795

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0810

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.0147

Gnomad4 SAS

AF:

0.0856

Gnomad4 FIN

AF:

0.0972

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.201

Hom.:

8023

Bravo

AF:

0.154

TwinsUK

AF:

0.218

AC:

809

ALSPAC

AF:

0.217

AC:

836

ESP6500AA

AF:

0.0836

AC:

368

ESP6500EA

AF:

0.215

AC:

1848

ExAC

AF:

0.149

AC:

18144

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

EpiCase

AF:

0.221

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NLRP14-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.041

Eigen_PC

Benign

-0.057

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.16

Sift

Benign

0.058

Sift4G

Pathogenic

0.0

Polyphen

0.71

Vest4

0.064

MPC

0.046

ClinPred

0.041

GERP RS

4.1

Varity_R

0.18

gMVP

0.20

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