rs2421047

Positions:

• chr5-159319299-G-A
• chr5-159319299-G-C
• chr5-159319299-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002187.3(IL12B):​c.698-406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,120 control chromosomes in the GnomAD database, including 5,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5591 hom., cov: 33)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12B	NM_002187.3	c.698-406C>T		intron_variant		ENST00000231228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12B	ENST00000231228.3	c.698-406C>T		intron_variant		1	NM_002187.3	P1
IL12B	ENST00000696750.1	c.68-406C>T		intron_variant
IL12B	ENST00000696751.1	c.*193-406C>T		intron_variant, NMD_transcript_variant
	ENST00000521472.6	n.290-6235G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39325 AN: 152002 Hom.: 5585 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39354 AN: 152120 Hom.: 5591 Cov.: 33 AF XY: 0.263 AC XY: 19539 AN XY: 74348

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.281

Alfa AF: 0.241 Hom.: 1029

Bravo AF: 0.274

Asia WGS AF: 0.432 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.59

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: rs2421047; hg19: chr5-158746307;