chr19-53793578-T-C

Position:

• chr19-53793578-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The variant allele was found at a frequency of 0.00123 in 197,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214

Genes affected

(HGNC:):

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-53793578-T-C is Benign according to our data. Variant chr19-53793578-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369290.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.53793578T>C		intergenic_region
NLRP12	NM_001277129.1	c.*471A>G		downstream_gene_variant			NP_001264058.1
NLRP12	XM_011527479.2	c.*471A>G		downstream_gene_variant			XP_011525781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 235 AN: 146612 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000559

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.000996

GnomAD4 exome AF: 0.000119 AC: 6 AN: 50456 Hom.: 0 Cov.: 0 AF XY: 0.000148 AC XY: 4 AN XY: 27056

Gnomad4 AFR exome AF: 0.00368

Gnomad4 AMR exome AF: 0.000278

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000335

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00161 AC: 236 AN: 146658 Hom.: 0 Cov.: 29 AF XY: 0.00163 AC XY: 116 AN XY: 71252

Gnomad4 AFR AF: 0.00565

Gnomad4 AMR AF: 0.000558

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.000990

Alfa AF: 0.000996 Hom.: 0

Bravo AF: 0.00192

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial cold autoinflammatory syndrome Benign:1

Likely 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	3.8
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs544178725; hg19: chr19-54296832;