chr5-159322080-G-T

Variant names:

• chr5-159322080-G-T
• rs2853694
• NM_002187.3:c.482+314C>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.482+314C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,964 control chromosomes in the GnomAD database, including 26,965 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 0.59 (26965 hom., cov: 31)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 57 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 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.482+314C>A		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.482+314C>A		intron	N/A	ENSP00000231228.2
	IL12B	ENST00000696750.1		c.-148-1560C>A		intron	N/A	ENSP00000512849.1
	ENSG00000249738	ENST00000521472.6	TSL:3	n.290-3454G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88894 AN: 151846 Hom.: 26914 Cov.: 31

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.586 AC: 89002 AN: 151964 Hom.: 26965 Cov.: 31 AF XY: 0.586 AC XY: 43527 AN XY: 74264

African (AFR) AF: 0.737 AC: 30560 AN: 41452

American (AMR) AF: 0.624 AC: 9535 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3501 AN: 5164

South Asian (SAS) AF: 0.548 AC: 2637 AN: 4814

European-Finnish (FIN) AF: 0.500 AC: 5267 AN: 10540

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33668 AN: 67936

Other (OTH) AF: 0.625 AC: 1318 AN: 2108

Alfa AF: 0.531 Hom.: 54774

Bravo AF: 0.608

Asia WGS AF: 0.667 AC: 2317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		-0.21
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: rs2853694; hg19: chr5-158749088;