rs11574790

chr5-159316838-G-A

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.856-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,612,714 control chromosomes in the GnomAD database, including 11,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1471 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9707 hom.)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.292

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=-0.74).
• BP6: Variant 5-159316838-G-A is Benign according to our data. Variant chr5-159316838-G-A is described in ClinVar as [Benign]. Clinvar id is 2628273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12B	NM_002187.3	c.856-22C>T		intron_variant		ENST00000231228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12B	ENST00000231228.3	c.856-22C>T		intron_variant		1	NM_002187.3	P1
IL12B	ENST00000696750.1	c.226-22C>T		intron_variant
IL12B	ENST00000696751.1	c.*351-22C>T		intron_variant, NMD_transcript_variant
	ENST00000521472.6	n.289+5424G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20124 AN: 152132 Hom.: 1464 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.0709

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.116 AC: 28627 AN: 245750 Hom.: 2026 AF XY: 0.111 AC XY: 14835 AN XY: 133172

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.0458

Gnomad SAS exome AF: 0.0708

Gnomad FIN exome AF: 0.0729

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.110 AC: 161074 AN: 1460464 Hom.: 9707 Cov.: 32 AF XY: 0.109 AC XY: 78930 AN XY: 726546

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0417

Gnomad4 SAS exome AF: 0.0715

Gnomad4 FIN exome AF: 0.0721

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.132 AC: 20148 AN: 152250 Hom.: 1471 Cov.: 33 AF XY: 0.128 AC XY: 9519 AN XY: 74432

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0709

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.141

Alfa AF: 0.127 Hom.: 1465

Bravo AF: 0.143

Asia WGS AF: 0.0680 AC: 237 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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	4.2
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11574790; hg19: chr5-158743846; COSMIC: COSV51455327; COSMIC: COSV51455327;