rs3212217

Positions:

• chr5-159328122-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000231228.3(IL12B):​c.1-1340G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,074 control chromosomes in the GnomAD database, including 5,769 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 0.26 (5769 hom., cov: 32)
• Consequence: IL12B ENST00000231228.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12B	NM_002187.3	c.1-1340G>C		intron_variant		ENST00000231228.3	NP_002178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.1-1340G>C		intron_variant		1	NM_002187.3	ENSP00000231228	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39998 AN: 151956 Hom.: 5763 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.263 AC: 40026 AN: 152074 Hom.: 5769 Cov.: 32 AF XY: 0.268 AC XY: 19928 AN XY: 74322

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.281

Alfa AF: 0.224 Hom.: 617

Bravo AF: 0.276

Asia WGS AF: 0.441 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.84
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212217; hg19: chr5-158755130;