19-53793980-G-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.*69C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,034,734 control chromosomes in the GnomAD database, including 3,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (402 hom., cov: 31)
  • Exomes 𝑓: 0.065 (2639 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.39

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=-1.02).
• BP6: Variant 19-53793980-G-T is Benign according to our data. Variant chr19-53793980-G-T is described in ClinVar as [Benign]. Clinvar id is 329997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP12	NM_144687.4	c.*69C>A		3_prime_UTR_variant	10/10	ENST00000324134.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP12	ENST00000324134.11	c.*69C>A		3_prime_UTR_variant	10/10	1	NM_144687.4	P4

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9663 AN: 151902 Hom.: 401 Cov.: 31

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0569

GnomAD4 exome AF: 0.0647 AC: 57102 AN: 882714 Hom.: 2639 Cov.: 12 AF XY: 0.0685 AC XY: 31730 AN XY: 463526

Gnomad4 AFR exome AF: 0.0729

Gnomad4 AMR exome AF: 0.0435

Gnomad4 ASJ exome AF: 0.0175

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.0241

Gnomad4 NFE exome AF: 0.0552

Gnomad4 OTH exome AF: 0.0653

GnomAD4 genome AF: 0.0637 AC: 9688 AN: 152020 Hom.: 402 Cov.: 31 AF XY: 0.0638 AC XY: 4737 AN XY: 74290

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0501 Hom.: 228

Bravo AF: 0.0625

Asia WGS AF: 0.212 AC: 737 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

clinical testing

GeneDx

May 14, 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	-1.0
Cadd	Benign	0.13
Dann	Benign	0.37

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: rs10410581; hg19: chr19-54297234; COSMIC: COSV60752417; COSMIC: COSV60752417;