chr19-53793724-AC-A

Position:

• chr19-53793724-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001277129.1(NLRP12):​c.*324del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17841 hom., cov: 0)
  • Exomes 𝑓: 0.46 (25705 hom.)
• Consequence: NLRP12 NM_001277129.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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 -10 ACMG points.

• BP6: Variant 19-53793724-AC-A is Benign according to our data. Variant chr19-53793724-AC-A is described in ClinVar as [Benign]. Clinvar id is 329988.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP12	NM_144687.4			downstream_gene_variant		ENST00000324134.11	NP_653288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP12	ENST00000324134.11			downstream_gene_variant		1	NM_144687.4	ENSP00000319377	P4

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72401 AN: 150128 Hom.: 17830 Cov.: 0

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.458 AC: 108513 AN: 236744 Hom.: 25705 Cov.: 0 AF XY: 0.459 AC XY: 58816 AN XY: 128190

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.482 AC: 72457 AN: 150242 Hom.: 17841 Cov.: 0 AF XY: 0.485 AC XY: 35554 AN XY: 73250

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.452

Alfa AF: 0.346 Hom.: 885

Bravo AF: 0.475

Asia WGS AF: 0.330 AC: 1149 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

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: rs34860841; hg19: chr19-54296978;