19-53805300-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144687.4(NLRP12):c.2394G>A(p.Gln798Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 1,613,798 control chromosomes in the GnomAD database, including 607,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 54876 hom., cov: 30)

Exomes 𝑓: 0.87 ( 552817 hom. )

Consequence

NLRP12
NM_144687.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.62

Variant links:

Genes affected

NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

NLRP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-53805300-C-T is Benign according to our data. Variant chr19-53805300-C-T is described in ClinVar as [Benign]. Clinvar id is 403242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53805300-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP12	NM_144687.4 link	c.2394G>A	p.Gln798Gln	synonymous_variant	Exon 5 of 10	ENST00000324134.11	NP_653288.1	P59046-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NLRP12	ENST00000324134.11 link	c.2394G>A	p.Gln798Gln	synonymous_variant	Exon 5 of 10	1	NM_144687.4	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9 link	c.2397G>A	p.Gln799Gln	synonymous_variant	Exon 5 of 9	1		ENSP00000341428.5	A0A0C4DH17
NLRP12	ENST00000391772.1 link	c.2397G>A	p.Gln799Gln	synonymous_variant	Exon 5 of 7	1		ENSP00000375652.1	A0A0C4DFY3

Frequencies

GnomAD3 genomes

AF:

0.849

AC:

128952

AN:

151962

Hom.:

54843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.865

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.800

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.855

GnomAD3 exomes

AF:

0.849

AC:

213437

AN:

251340

Hom.:

91026

AF XY:

0.849

AC XY:

115380

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.796

Gnomad AMR exome

AF:

0.839

Gnomad ASJ exome

AF:

0.854

Gnomad EAS exome

AF:

0.747

Gnomad SAS exome

AF:

0.798

Gnomad FIN exome

AF:

0.886

Gnomad NFE exome

AF:

0.882

Gnomad OTH exome

AF:

0.858

GnomAD4 exome

AF:

0.868

AC:

1269291

AN:

1461718

Hom.:

552817

Cov.:

AF XY:

0.866

AC XY:

630022

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.788

Gnomad4 AMR exome

AF:

0.842

Gnomad4 ASJ exome

AF:

0.855

Gnomad4 EAS exome

AF:

0.690

Gnomad4 SAS exome

AF:

0.797

Gnomad4 FIN exome

AF:

0.885

Gnomad4 NFE exome

AF:

0.884

Gnomad4 OTH exome

AF:

0.860

GnomAD4 genome

AF:

0.849

AC:

129042

AN:

152080

Hom.:

54876

Cov.:

AF XY:

0.849

AC XY:

63086

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.796

Gnomad4 AMR

AF:

0.866

Gnomad4 ASJ

AF:

0.856

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.800

Gnomad4 FIN

AF:

0.891

Gnomad4 NFE

AF:

0.881

Gnomad4 OTH

AF:

0.852

Alfa

AF:

0.870

Hom.:

127155

Bravo

AF:

0.844

Asia WGS

AF:

0.788

AC:

2739

AN:

3478

EpiCase

AF:

0.873

EpiControl

AF:

0.874

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial cold autoinflammatory syndrome 2

Benign:3

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.032

DANN

Benign

0.42

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