1-67389364-G-C

Variant names:

• chr1-67389364-G-C
• rs2172962
• NM_001374259.2:c.1947-665G>C

Variant summary

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

The NM_001374259.2(IL12RB2):​c.1947-665G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,306 control chromosomes in the GnomAD database, including 18,690 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 0.47 (18690 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.1947-665G>C		intron_variant	Intron 15 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.1947-665G>C		intron_variant	Intron 15 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70799 AN: 151190 Hom.: 18687 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.468 AC: 70808 AN: 151306 Hom.: 18690 Cov.: 32 AF XY: 0.474 AC XY: 34968 AN XY: 73818

African (AFR) AF: 0.230 AC: 9463 AN: 41222

American (AMR) AF: 0.464 AC: 7058 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1542 AN: 3460

East Asian (EAS) AF: 0.344 AC: 1766 AN: 5138

South Asian (SAS) AF: 0.564 AC: 2711 AN: 4810

European-Finnish (FIN) AF: 0.696 AC: 7192 AN: 10338

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39502 AN: 67830

Other (OTH) AF: 0.447 AC: 938 AN: 2098

Alfa AF: 0.519 Hom.: 2675

Bravo AF: 0.435

Asia WGS AF: 0.390 AC: 1354 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.57
PhyloP100		-0.85
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: rs2172962; hg19: chr1-67855047; COSMIC: COSV52022081;