rs12150220

Positions:

chr17-5582047-A-T

Variant summary

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

The NM_033004.4(NLRP1):c.464T>A(p.Leu155His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,610,836 control chromosomes in the GnomAD database, including 142,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 10309 hom., cov: 32)

Exomes 𝑓: 0.41 ( 132420 hom. )

Consequence

NLRP1
NM_033004.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

NLRP1 (HGNC:14374): (NLR family pyrin domain containing 1) This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

NLRP1 links:

NLRP1 (HGNC:):

NLRP1 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=1.975894E-4).

BP6

Variant 17-5582047-A-T is Benign according to our data. Variant chr17-5582047-A-T is described in ClinVar as [Benign]. Clinvar id is 4163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP1	NM_033004.4 linkuse as main transcript	c.464T>A	p.Leu155His	missense_variant	3/17	ENST00000572272.6	NP_127497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP1	ENST00000572272.6 linkuse as main transcript	c.464T>A	p.Leu155His	missense_variant	3/17	1	NM_033004.4	ENSP00000460475.1		Q9C000-1

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

49953

AN:

151962

Hom.:

10308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.0295

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.366

AC:

90395

AN:

246982

Hom.:

19305

AF XY:

0.366

AC XY:

48923

AN XY:

133754

show subpopulations

Gnomad AFR exome

AF:

0.0912

Gnomad AMR exome

AF:

0.417

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.0251

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.457

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.414

AC:

603617

AN:

1458756

Hom.:

132420

Cov.:

AF XY:

0.410

AC XY:

297448

AN XY:

725724

show subpopulations

Gnomad4 AFR exome

AF:

0.0846

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.472

Gnomad4 EAS exome

AF:

0.0322

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.450

Gnomad4 OTH exome

AF:

0.386

GnomAD4 genome

AF:

0.329

AC:

49963

AN:

152080

Hom.:

10309

Cov.:

AF XY:

0.327

AC XY:

24306

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.0295

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.427

Hom.:

11161

Bravo

AF:

0.314

TwinsUK

AF:

0.431

AC:

1598

ALSPAC

AF:

0.464

AC:

1790

ESP6500AA

AF:

0.0992

AC:

437

ESP6500EA

AF:

0.452

AC:

3884

ExAC

AF:

0.359

AC:

43605

Asia WGS

AF:

0.142

AC:

497

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Respiratory papillomatosis, juvenile recurrent, congenital

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Autoinflammation with arthritis and dyskeratosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Vitiligo-associated multiple autoimmune disease susceptibility 1

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 22, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.8

DANN

Benign

0.89

DEOGEN2

Benign

0.0084

.;.;.;.;T;.;.;.;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.59

.;T;.;.;.;.;T;T;T;T

MetaRNN

Benign

0.00020

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.43

N;.;.;N;.;N;.;.;.;N

REVEL

Benign

0.084

Sift

Benign

0.060

T;.;.;T;.;T;.;.;.;T

Sift4G

Benign

0.42

T;T;.;T;T;T;T;T;T;T

Polyphen

1.0, 0.99

.;.;D;D;D;D;D;D;D;D

Vest4

0.11

MPC

0.49

ClinPred

0.013

GERP RS

-1.1

Varity_R

0.049

gMVP

0.26

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