rs946685

chr1-67350032-A-G

Variant summary

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

The NM_001374259.2(IL12RB2):c.1039-838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,072 control chromosomes in the GnomAD database, including 38,541 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 0.67 (38541 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB2	NM_001374259.2	c.1039-838A>G		intron_variant		ENST00000674203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB2	ENST00000674203.2	c.1039-838A>G		intron_variant			NM_001374259.2	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102572 AN: 151954 Hom.: 38547 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.675 AC: 102583 AN: 152072 Hom.: 38541 Cov.: 32 AF XY: 0.684 AC XY: 50837 AN XY: 74344

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.683

Alfa AF: 0.710 Hom.: 5493

Bravo AF: 0.642

Asia WGS AF: 0.744 AC: 2587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	12
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs946685; hg19: chr1-67815715;