rs10749775

Variant names:

• chr1-67356404-C-A
• rs10749775
• NM_001374259.2:c.1258+5315C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-67356404-C-A
• chr1-67356404-C-G
• chr1-67356404-C-T

Variant summary

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

The NM_001374259.2(IL12RB2):​c.1258+5315C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,164 control chromosomes in the GnomAD database, including 51,363 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 0.81 (51363 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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.1258+5315C>A		intron	N/A	NP_001361188.1	Q99665-1
	IL12RB2	NM_001559.3		c.1258+5315C>A		intron	N/A	NP_001550.1	Q99665-1
	IL12RB2	NM_001258215.1		c.1258+5315C>A		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.1258+5315C>A		intron	N/A	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000262345.5	TSL:1	c.1258+5315C>A		intron	N/A	ENSP00000262345.1	Q99665-1
	IL12RB2	ENST00000544434.5	TSL:1	c.1258+5315C>A		intron	N/A	ENSP00000442443.1	Q99665-3

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123191 AN: 152046 Hom.: 51345 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.810 AC: 123258 AN: 152164 Hom.: 51363 Cov.: 32 AF XY: 0.818 AC XY: 60832 AN XY: 74380

African (AFR) AF: 0.590 AC: 24471 AN: 41454

American (AMR) AF: 0.890 AC: 13609 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3014 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5149 AN: 5180

South Asian (SAS) AF: 0.948 AC: 4563 AN: 4812

European-Finnish (FIN) AF: 0.943 AC: 10004 AN: 10614

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59631 AN: 68020

Other (OTH) AF: 0.829 AC: 1755 AN: 2116

Alfa AF: 0.838 Hom.: 11334

Bravo AF: 0.793

Asia WGS AF: 0.923 AC: 3210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.36
PhyloP100		0.41
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: rs10749775; hg19: chr1-67822087;