1-67348757-T-C

Variant names:

• chr1-67348757-T-C
• rs3790566
• NM_001374259.2:c.1039-2113T>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.1039-2113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,062 control chromosomes in the GnomAD database, including 32,808 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 0.62 (32808 hom., cov: 31)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 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.1039-2113T>C		intron	N/A	NP_001361188.1
	IL12RB2	NM_001559.3		c.1039-2113T>C		intron	N/A	NP_001550.1
	IL12RB2	NM_001258215.1		c.1039-2113T>C		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.1039-2113T>C		intron	N/A	ENSP00000501329.1
	IL12RB2	ENST00000262345.5	TSL:1	c.1039-2113T>C		intron	N/A	ENSP00000262345.1
	IL12RB2	ENST00000544434.5	TSL:1	c.1039-2113T>C		intron	N/A	ENSP00000442443.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93942 AN: 151946 Hom.: 32810 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.618 AC: 93950 AN: 152062 Hom.: 32808 Cov.: 31 AF XY: 0.626 AC XY: 46568 AN XY: 74334

African (AFR) AF: 0.272 AC: 11269 AN: 41472

American (AMR) AF: 0.666 AC: 10167 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2059 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3798 AN: 5172

South Asian (SAS) AF: 0.775 AC: 3736 AN: 4818

European-Finnish (FIN) AF: 0.868 AC: 9180 AN: 10578

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.758 AC: 51504 AN: 67970

Other (OTH) AF: 0.622 AC: 1314 AN: 2114

Alfa AF: 0.709 Hom.: 154197

Bravo AF: 0.583

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.092
DANN	Benign	0.58
PhyloP100		-2.2
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: rs3790566; hg19: chr1-67814440; COSMIC: COSV52021727;