NM_001374259.2:c.479+639C>G

Variant names:

• chr1-67327488-C-G
• rs10489626
• NM_001374259.2:c.479+639C>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.479+639C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,030 control chromosomes in the GnomAD database, including 2,241 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 0.17 (2241 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	NM_001374259.2	MANE Select	c.479+639C>G		intron	N/A	NP_001361188.1
	IL12RB2	NM_001559.3		c.479+639C>G		intron	N/A	NP_001550.1
	IL12RB2	NM_001258215.1		c.479+639C>G		intron	N/A	NP_001245144.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.479+639C>G		intron	N/A	ENSP00000501329.1
	IL12RB2	ENST00000262345.5	TSL:1	c.479+639C>G		intron	N/A	ENSP00000262345.1
	IL12RB2	ENST00000544434.5	TSL:1	c.479+639C>G		intron	N/A	ENSP00000442443.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25567 AN: 151912 Hom.: 2234 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.168 AC: 25604 AN: 152030 Hom.: 2241 Cov.: 32 AF XY: 0.163 AC XY: 12148 AN XY: 74324

African (AFR) AF: 0.201 AC: 8347 AN: 41454

American (AMR) AF: 0.160 AC: 2451 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3468

East Asian (EAS) AF: 0.0577 AC: 299 AN: 5180

South Asian (SAS) AF: 0.112 AC: 537 AN: 4808

European-Finnish (FIN) AF: 0.0781 AC: 823 AN: 10544

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11617 AN: 67988

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.103 Hom.: 168

Bravo AF: 0.178

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.42
PhyloP100		-1.6
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: rs10489626; hg19: chr1-67793171;