rs2546893

Variant names:

• chr5-159328952-G-A
• rs2546893
• NM_002187.3:c.-1+1480C>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.-1+1480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,002 control chromosomes in the GnomAD database, including 14,368 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 0.42 (14368 hom., cov: 32)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 29 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3	c.-1+1480C>T		intron_variant	Intron 1 of 7	ENST00000231228.3	NP_002178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.-1+1480C>T		intron_variant	Intron 1 of 7	1	NM_002187.3	ENSP00000231228.2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64375 AN: 151884 Hom.: 14368 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.424 AC: 64383 AN: 152002 Hom.: 14368 Cov.: 32 AF XY: 0.425 AC XY: 31572 AN XY: 74282

African (AFR) AF: 0.272 AC: 11293 AN: 41450

American (AMR) AF: 0.416 AC: 6363 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1683 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2516 AN: 5160

South Asian (SAS) AF: 0.453 AC: 2180 AN: 4814

European-Finnish (FIN) AF: 0.481 AC: 5071 AN: 10552

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33826 AN: 67958

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.456 Hom.: 24378

Bravo AF: 0.408

Asia WGS AF: 0.425 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.31
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: rs2546893; hg19: chr5-158755960;