Genetic Variant NLRP12:c.-140T>A (chr19-53824314-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_144687.4(NLRP12):c.-140T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 813,216 control chromosomes in the GnomAD database, including 249,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47053 hom., cov: 30)

Exomes 𝑓: 0.78 ( 202906 hom. )

Consequence

NLRP12
NM_144687.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-53824314-A-T is Benign according to our data. Variant chr19-53824314-A-T is described in ClinVar as [Benign]. Clinvar id is 330052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53824314-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP12	NM_144687.4 link	c.-140T>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000324134.11	NP_653288.1	P59046-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NLRP12	ENST00000324134.11 link	c.-140T>A	5_prime_UTR_variant	Exon 1 of 10	1	NM_144687.4	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9 link	c.-140T>A	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000341428.5	A0A0C4DH17
NLRP12	ENST00000391772.1 link	c.-140T>A	5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000375652.1	A0A0C4DFY3

Frequencies

GnomAD3 genomes

AF:

0.787

AC:

119457

AN:

151840

Hom.:

47000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.815

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.789

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.799

GnomAD4 exome

AF:

0.783

AC:

517809

AN:

661258

Hom.:

202906

Cov.:

AF XY:

0.784

AC XY:

271382

AN XY:

346186

show subpopulations

Gnomad4 AFR exome

AF:

0.788

Gnomad4 AMR exome

AF:

0.743

Gnomad4 ASJ exome

AF:

0.817

Gnomad4 EAS exome

AF:

0.753

Gnomad4 SAS exome

AF:

0.792

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.786

Gnomad4 OTH exome

AF:

0.783

GnomAD4 genome

AF:

0.787

AC:

119564

AN:

151958

Hom.:

47053

Cov.:

AF XY:

0.786

AC XY:

58348

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.795

Gnomad4 AMR

AF:

0.756

Gnomad4 ASJ

AF:

0.815

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.788

Gnomad4 FIN

AF:

0.760

Gnomad4 NFE

AF:

0.794

Gnomad4 OTH

AF:

0.793

Alfa

AF:

0.788

Hom.:

4858

Bravo

AF:

0.786

Asia WGS

AF:

0.735

AC:

2559

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

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 93% of patients studied by a panel of primary immunodeficiencies. Number of patients: 89. Only high quality variants are reported. -

Familial cold autoinflammatory syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.48

DANN

Benign

0.36

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