1-67365611-G-C

Variant names:

• chr1-67365611-G-C
• rs12564159
• NM_001374259.2:c.1259-2214G>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.1259-2214G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,960 control chromosomes in the GnomAD database, including 33,034 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 0.65 (33034 hom., cov: 31)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 11 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.1259-2214G>C		intron_variant	Intron 10 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.1259-2214G>C		intron_variant	Intron 10 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99229 AN: 151844 Hom.: 33016 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.653 AC: 99291 AN: 151960 Hom.: 33034 Cov.: 31 AF XY: 0.659 AC XY: 48916 AN XY: 74266

African (AFR) AF: 0.525 AC: 21716 AN: 41394

American (AMR) AF: 0.687 AC: 10487 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2445 AN: 3464

East Asian (EAS) AF: 0.606 AC: 3136 AN: 5172

South Asian (SAS) AF: 0.730 AC: 3512 AN: 4812

European-Finnish (FIN) AF: 0.771 AC: 8147 AN: 10570

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47695 AN: 67964

Other (OTH) AF: 0.654 AC: 1383 AN: 2116

Alfa AF: 0.681 Hom.: 4446

Bravo AF: 0.637

Asia WGS AF: 0.637 AC: 2216 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	1.6
DANN	Benign	0.68
PhyloP100		-0.33
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: rs12564159; hg19: chr1-67831294;