5-159323971-C-T

Variant names:

• chr5-159323971-C-T
• rs3213093
• NM_002187.3:c.89-642G>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.89-642G>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 151,110 control chromosomes in the GnomAD database, including 5,874 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 (5874 hom., cov: 30)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689
• Publications: 6 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000249738 (HGNC:58156):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3	c.89-642G>A		intron_variant	Intron 2 of 7	ENST00000231228.3	NP_002178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.89-642G>A		intron_variant	Intron 2 of 7	1	NM_002187.3	ENSP00000231228.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40085 AN: 151020 Hom.: 5868 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.285

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: 40114 AN: 151110 Hom.: 5874 Cov.: 30 AF XY: 0.270 AC XY: 19889 AN XY: 73718

African (AFR) AF: 0.340 AC: 13947 AN: 41034

American (AMR) AF: 0.333 AC: 5076 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2451 AN: 5172

South Asian (SAS) AF: 0.363 AC: 1739 AN: 4792

European-Finnish (FIN) AF: 0.180 AC: 1833 AN: 10206

Middle Eastern (MID) AF: 0.281 AC: 81 AN: 288

European-Non Finnish (NFE) AF: 0.201 AC: 13627 AN: 67914

Other (OTH) AF: 0.287 AC: 603 AN: 2102

Alfa AF: 0.215 Hom.: 1097

Bravo AF: 0.282

Asia WGS AF: 0.437 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-0.69
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: rs3213093; hg19: chr5-158750979;