rs2030071

Positions:

• chr1-67313241-G-A

Variant summary

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

The NM_001374259.2(IL12RB2):​c.-124-672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,312 control chromosomes in the GnomAD database, including 168 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 0.046 (168 hom., cov: 33)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.-124-672G>A		intron_variant		ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.-124-672G>A		intron_variant			NM_001374259.2	ENSP00000501329	P1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6929 AN: 152194 Hom.: 167 Cov.: 33

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0455 AC: 6937 AN: 152312 Hom.: 168 Cov.: 33 AF XY: 0.0453 AC XY: 3377 AN XY: 74474

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0554

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0439 Hom.: 34

Bravo AF: 0.0499

Asia WGS AF: 0.0740 AC: 258 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	0.041
DANN	Benign	0.83

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: rs2030071; hg19: chr1-67778924;