rs2421047

Variant names:

• chr5-159319299-G-A
• rs2421047
• NM_002187.3:c.698-406C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

IL12B Gene-Disease associations (from GenCC):

• Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

IL12B-AS1 (HGNC:58156):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002187.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	NM_002187.3	MANE Select	c.698-406C>T		intron	N/A	NP_002178.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	ENST00000231228.3	TSL:1 MANE Select	c.698-406C>T		intron	N/A	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.68-406C>T		intron	N/A	ENSP00000512849.1	A0A8Q3WML5
	IL12B-AS1	ENST00000521472.6	TSL:3	n.290-6235G>A		intron	N/A

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

African (AFR) AF: 0.318 AC: 13192 AN: 41496

American (AMR) AF: 0.332 AC: 5067 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2405 AN: 5174

South Asian (SAS) AF: 0.363 AC: 1752 AN: 4828

European-Finnish (FIN) AF: 0.179 AC: 1890 AN: 10580

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13616 AN: 67990

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.253 Hom.: 1317

Bravo AF: 0.274

Asia WGS AF: 0.432 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.59
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2421047; hg19: chr5-158746307;