rs3790558

Variant names:

• chr1-67311338-G-T
• rs3790558
• NM_001374259.2:c.-124-2575G>T

Variant summary

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

The NM_001374259.2(IL12RB2):​c.-124-2575G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,970 control chromosomes in the GnomAD database, including 17,645 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 0.45 (17645 hom., cov: 31)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 15 publications found

Genes affected

IL12RB2 (HGNC:5972): (interleukin 12 receptor subunit beta 2) The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.-124-2575G>T		intron_variant	Intron 1 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.-124-2575G>T		intron_variant	Intron 1 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68117 AN: 151852 Hom.: 17650 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.448 AC: 68116 AN: 151970 Hom.: 17645 Cov.: 31 AF XY: 0.457 AC XY: 33926 AN XY: 74256

African (AFR) AF: 0.184 AC: 7627 AN: 41482

American (AMR) AF: 0.455 AC: 6944 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1700 AN: 3466

East Asian (EAS) AF: 0.540 AC: 2783 AN: 5150

South Asian (SAS) AF: 0.544 AC: 2615 AN: 4804

European-Finnish (FIN) AF: 0.689 AC: 7270 AN: 10556

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37626 AN: 67926

Other (OTH) AF: 0.419 AC: 883 AN: 2106

Alfa AF: 0.509 Hom.: 37985

Bravo AF: 0.417

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.34
PhyloP100		-2.2
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: rs3790558; hg19: chr1-67777021; COSMIC: COSV52021486;