chr5-159328558-C-T

Variant names:

• chr5-159328558-C-T
• rs1003199
• NM_002187.3:c.1-1776G>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.1-1776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,036 control chromosomes in the GnomAD database, including 14,700 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 0.43 (14700 hom., cov: 32)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 31 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 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.1-1776G>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.1-1776G>A		intron	N/A	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.-149+1874G>A		intron	N/A	ENSP00000512849.1	A0A8Q3WML5
	IL12B-AS1	ENST00000521472.6	TSL:3	n.410+2904C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64865 AN: 151916 Hom.: 14700 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.427 AC: 64881 AN: 152036 Hom.: 14700 Cov.: 32 AF XY: 0.430 AC XY: 31921 AN XY: 74296

African (AFR) AF: 0.280 AC: 11614 AN: 41474

American (AMR) AF: 0.387 AC: 5908 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1667 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1992 AN: 5174

South Asian (SAS) AF: 0.436 AC: 2096 AN: 4812

European-Finnish (FIN) AF: 0.580 AC: 6127 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34015 AN: 67954

Other (OTH) AF: 0.409 AC: 864 AN: 2110

Alfa AF: 0.458 Hom.: 27766

Bravo AF: 0.401

Asia WGS AF: 0.391 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.87
DANN	Benign	0.41
PhyloP100		-0.14
Mutation Taster		=96/4	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: rs1003199; hg19: chr5-158755566;