chr5-159316395-T-G

Variant names:

• chr5-159316395-T-G
• rs2853697
• NM_002187.3:c.987+290A>C

Variant summary

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

The NM_002187.3(IL12B):​c.987+290A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,240 control chromosomes in the GnomAD database, including 1,960 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 0.15 (1960 hom., cov: 33)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 14 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 (NFE) allele frequency at 95% confidence interval = 0.181 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.987+290A>C		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.987+290A>C		intron	N/A	ENSP00000231228.2
	IL12B	ENST00000696750.1		c.357+290A>C		intron	N/A	ENSP00000512849.1
	ENSG00000249738	ENST00000521472.6	TSL:3	n.289+4981T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22897 AN: 152122 Hom.: 1956 Cov.: 33

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.150 AC: 22909 AN: 152240 Hom.: 1960 Cov.: 33 AF XY: 0.152 AC XY: 11347 AN XY: 74438

African (AFR) AF: 0.0749 AC: 3112 AN: 41568

American (AMR) AF: 0.127 AC: 1943 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3464

East Asian (EAS) AF: 0.172 AC: 892 AN: 5186

South Asian (SAS) AF: 0.119 AC: 576 AN: 4822

European-Finnish (FIN) AF: 0.248 AC: 2629 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12519 AN: 67998

Other (OTH) AF: 0.166 AC: 350 AN: 2114

Alfa AF: 0.147 Hom.: 495

Bravo AF: 0.140

Asia WGS AF: 0.149 AC: 520 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	0.27
DANN	Benign	0.74
PhyloP100		-1.0
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: rs2853697; hg19: chr5-158743403;