19-53824314-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.38

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]

ACMG classification

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/exons	MANE	UniProt
NLRP12	NM_144687.4	c.-140T>A		5_prime_UTR_variant	1/10	ENST00000324134.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP12	ENST00000324134.11	c.-140T>A		5_prime_UTR_variant	1/10	1	NM_144687.4	P4

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119457 AN: 151840 Hom.: 47000 Cov.: 30

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.: 9 AF XY: 0.784 AC XY: 271382 AN XY: 346186

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.: 30 AF XY: 0.786 AC XY: 58348 AN XY: 74264

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Familial cold autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

Other links and lift over

dbSNP: rs4419163; hg19: chr19-54327568; COSMIC: COSV60757137;