chr1-67389459-T-G

Variant names:

• chr1-67389459-T-G
• rs11209063
• NM_001374259.2:c.1947-570T>G

Variant summary

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

The NM_001374259.2(IL12RB2):​c.1947-570T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,246 control chromosomes in the GnomAD database, including 3,390 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 0.19 (3390 hom., cov: 34)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374259.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	NM_001374259.2	MANE Select	c.1947-570T>G		intron	N/A	NP_001361188.1	Q99665-1
	IL12RB2	NM_001559.3		c.1947-570T>G		intron	N/A	NP_001550.1	Q99665-1
	IL12RB2	NM_001258215.1		c.1689-570T>G		intron	N/A	NP_001245144.1	Q99665-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.1947-570T>G		intron	N/A	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000262345.5	TSL:1	c.1947-570T>G		intron	N/A	ENSP00000262345.1	Q99665-1
	IL12RB2	ENST00000544434.5	TSL:1	c.1689-570T>G		intron	N/A	ENSP00000442443.1	Q99665-3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29265 AN: 152128 Hom.: 3375 Cov.: 34

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.193 AC: 29322 AN: 152246 Hom.: 3390 Cov.: 34 AF XY: 0.191 AC XY: 14207 AN XY: 74450

African (AFR) AF: 0.301 AC: 12495 AN: 41506

American (AMR) AF: 0.231 AC: 3535 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1358 AN: 5194

South Asian (SAS) AF: 0.167 AC: 806 AN: 4828

European-Finnish (FIN) AF: 0.0802 AC: 851 AN: 10614

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8763 AN: 68012

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.151 Hom.: 6595

Bravo AF: 0.210

Asia WGS AF: 0.249 AC: 867 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.78
PhyloP100		0.23
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: rs11209063; hg19: chr1-67855142;