rs919766

chr5-159320556-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002187.3(IL12B):c.483-36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,547,022 control chromosomes in the GnomAD database, including 11,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1811 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9562 hom.)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.248

Genes affected

IL12B (HGNC:5970): (interleukin 12B) This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-159320556-A-C is Benign according to our data. Variant chr5-159320556-A-C is described in ClinVar as [Benign]. Clinvar id is 2628262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12B	NM_002187.3	c.483-36T>G		intron_variant		ENST00000231228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12B	ENST00000231228.3	c.483-36T>G		intron_variant		1	NM_002187.3	P1
IL12B	ENST00000696750.1	c.-148-36T>G		intron_variant
IL12B	ENST00000696751.1	c.365-36T>G		intron_variant, NMD_transcript_variant
	ENST00000521472.6	n.290-4978A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21409 AN: 152126 Hom.: 1796 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.119 AC: 29470 AN: 247156 Hom.: 2135 AF XY: 0.114 AC XY: 15202 AN XY: 133880

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0460

Gnomad SAS exome AF: 0.0712

Gnomad FIN exome AF: 0.0726

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.111 AC: 155515 AN: 1394778 Hom.: 9562 Cov.: 23 AF XY: 0.110 AC XY: 76610 AN XY: 697870

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0415

Gnomad4 SAS exome AF: 0.0715

Gnomad4 FIN exome AF: 0.0719

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.141 AC: 21455 AN: 152244 Hom.: 1811 Cov.: 32 AF XY: 0.136 AC XY: 10140 AN XY: 74432

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.147

Alfa AF: 0.131 Hom.: 492

Bravo AF: 0.153

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.53
Dann	Benign	0.48

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: rs919766; hg19: chr5-158747564;