rs11651270

Positions:

chr17-5521757-T-C

Variant summary

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

The NM_033004.4(NLRP1):c.3550A>G(p.Met1184Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,610,340 control chromosomes in the GnomAD database, including 169,620 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 0.47 ( 17007 hom., cov: 32)

Exomes 𝑓: 0.46 ( 152613 hom. )

Consequence

NLRP1
NM_033004.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.546

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:

LOC124903902 (HGNC:):

LOC124903902 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=3.0520558E-4).

BP6

Variant 17-5521757-T-C is Benign according to our data. Variant chr17-5521757-T-C is described in ClinVar as [Benign]. Clinvar id is 403240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP1	NM_033004.4 link	c.3550A>G	p.Met1184Val	missense_variant	13/17	ENST00000572272.6	NP_127497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP1	ENST00000572272.6 link	c.3550A>G	p.Met1184Val	missense_variant	13/17	1	NM_033004.4	ENSP00000460475.1		Q9C000-1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71404

AN:

151966

Hom.:

16966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.458

GnomAD3 exomes

AF:

0.449

AC:

112339

AN:

250088

Hom.:

25870

AF XY:

0.448

AC XY:

60512

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.512

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.424

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.468

GnomAD4 exome

AF:

0.455

AC:

663905

AN:

1458256

Hom.:

152613

Cov.:

AF XY:

0.455

AC XY:

329807

AN XY:

725370

show subpopulations

Gnomad4 AFR exome

AF:

0.511

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.518

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.464

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.470

AC:

71509

AN:

152084

Hom.:

17007

Cov.:

AF XY:

0.470

AC XY:

34949

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.507

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.513

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.422

Gnomad4 FIN

AF:

0.468

Gnomad4 NFE

AF:

0.467

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.464

Hom.:

41251

Bravo

AF:

0.469

TwinsUK

AF:

0.441

AC:

1635

ALSPAC

AF:

0.466

AC:

1797

ESP6500AA

AF:

0.510

AC:

2249

ESP6500EA

AF:

0.468

AC:

4028

ExAC

AF:

0.452

AC:

54869

Asia WGS

AF:

0.408

AC:

1417

AN:

3478

EpiCase

AF:

0.465

EpiControl

AF:

0.464

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 14, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.34

DEOGEN2

Benign

0.0035

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00088

LIST_S2

Benign

0.48

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

MetaRNN

Benign

0.00031

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

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.37

PROVEAN

Benign

1.8

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

REVEL

Benign

0.071

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

.;.;B;B;B;B;B;B;B;B

Vest4

0.055

MPC

0.21

ClinPred

0.0020

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.035

gMVP

0.31

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