chr5-159317652-T-C

Variant names:

• chr5-159317652-T-C
• rs2853696
• NM_002187.3:c.856-836A>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.856-836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,270 control chromosomes in the GnomAD database, including 58,187 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 0.87 (58187 hom., cov: 33)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3	c.856-836A>G		intron_variant	Intron 6 of 7	ENST00000231228.3	NP_002178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.856-836A>G		intron_variant	Intron 6 of 7	1	NM_002187.3	ENSP00000231228.2

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132734 AN: 152152 Hom.: 58126 Cov.: 33

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.872 AC: 132855 AN: 152270 Hom.: 58187 Cov.: 33 AF XY: 0.876 AC XY: 65213 AN XY: 74426

African (AFR) AF: 0.944 AC: 39221 AN: 41554

American (AMR) AF: 0.896 AC: 13704 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2935 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5180 AN: 5188

South Asian (SAS) AF: 0.869 AC: 4188 AN: 4820

European-Finnish (FIN) AF: 0.858 AC: 9097 AN: 10600

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55658 AN: 68024

Other (OTH) AF: 0.882 AC: 1865 AN: 2114

Alfa AF: 0.876 Hom.: 16626

Bravo AF: 0.881

Asia WGS AF: 0.943 AC: 3282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.47
PhyloP100		-1.8
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: rs2853696; hg19: chr5-158744660;