5-159323985-T-C

Variant names:

• chr5-159323985-T-C
• rs2569253
• NM_002187.3:c.89-656A>G

Variant summary

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

The NM_002187.3(IL12B):​c.89-656A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,822 control chromosomes in the GnomAD database, including 15,027 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 (15027 hom., cov: 30)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 28 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	NM_002187.3	MANE Select	c.89-656A>G		intron	N/A	NP_002178.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	ENST00000231228.3	TSL:1 MANE Select	c.89-656A>G		intron	N/A	ENSP00000231228.2
	IL12B	ENST00000696750.1		c.-148-3465A>G		intron	N/A	ENSP00000512849.1
	ENSG00000249738	ENST00000521472.6	TSL:3	n.290-1549T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64984 AN: 151712 Hom.: 15027 Cov.: 30

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.428 AC: 65006 AN: 151822 Hom.: 15027 Cov.: 30 AF XY: 0.433 AC XY: 32162 AN XY: 74204

African (AFR) AF: 0.257 AC: 10642 AN: 41370

American (AMR) AF: 0.391 AC: 5968 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2502 AN: 5168

South Asian (SAS) AF: 0.440 AC: 2120 AN: 4818

European-Finnish (FIN) AF: 0.609 AC: 6393 AN: 10492

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34227 AN: 67938

Other (OTH) AF: 0.412 AC: 869 AN: 2108

Alfa AF: 0.464 Hom.: 10115

Bravo AF: 0.402

Asia WGS AF: 0.426 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.27
PhyloP100		-1.2
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: rs2569253; hg19: chr5-158750993;