5-159323761-C-T

Variant names:

• chr5-159323761-C-T
• rs3213094
• NM_002187.3:c.89-432G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002187.3(IL12B):​c.89-432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,866 control chromosomes in the GnomAD database, including 5,924 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 0.27 (5924 hom., cov: 31)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 86 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 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.89-432G>A		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.89-432G>A		intron	N/A	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.-148-3241G>A		intron	N/A	ENSP00000512849.1	A0A8Q3WML5
	IL12B-AS1	ENST00000521472.6	TSL:3	n.290-1773C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40282 AN: 151748 Hom.: 5918 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.265 AC: 40312 AN: 151866 Hom.: 5924 Cov.: 31 AF XY: 0.270 AC XY: 20011 AN XY: 74206

African (AFR) AF: 0.340 AC: 14068 AN: 41380

American (AMR) AF: 0.334 AC: 5092 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2445 AN: 5150

South Asian (SAS) AF: 0.362 AC: 1741 AN: 4810

European-Finnish (FIN) AF: 0.179 AC: 1890 AN: 10538

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

European-Non Finnish (NFE) AF: 0.201 AC: 13633 AN: 67952

Other (OTH) AF: 0.286 AC: 603 AN: 2106

Alfa AF: 0.232 Hom.: 19580

Bravo AF: 0.282

Asia WGS AF: 0.438 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.75
PhyloP100		-0.92
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: rs3213094; hg19: chr5-158750769;