19-53793783-C-A

Position:

• chr19-53793783-C-A

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.*266G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 548,544 control chromosomes in the GnomAD database, including 1,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (340 hom., cov: 30)
  • Exomes 𝑓: 0.069 (1396 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-53793783-C-A is Benign according to our data. Variant chr19-53793783-C-A is described in ClinVar as [Benign]. Clinvar id is 329990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP12	NM_144687.4	c.*266G>T		3_prime_UTR_variant	10/10	ENST00000324134.11	NP_653288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP12	ENST00000324134.11	c.*266G>T		3_prime_UTR_variant	10/10	1	NM_144687.4	ENSP00000319377	P4

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8722 AN: 151670 Hom.: 338 Cov.: 30

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0525

GnomAD4 exome AF: 0.0685 AC: 27192 AN: 396756 Hom.: 1396 Cov.: 0 AF XY: 0.0732 AC XY: 15424 AN XY: 210728

Gnomad4 AFR exome AF: 0.0543

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0549

Gnomad4 OTH exome AF: 0.0633

GnomAD4 genome AF: 0.0576 AC: 8744 AN: 151788 Hom.: 340 Cov.: 30 AF XY: 0.0579 AC XY: 4291 AN XY: 74166

Gnomad4 AFR AF: 0.0535

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.0567

Alfa AF: 0.0527 Hom.: 30

Bravo AF: 0.0552

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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	1.9
DANN	Benign	0.45

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: rs10409778; hg19: chr19-54297037;