rs2201584

Variant names:

• chr1-67322032-G-A
• rs2201584
• NM_001374259.2:c.364+143G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-67322032-G-A
• chr1-67322032-G-C
• chr1-67322032-G-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.364+143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 744,366 control chromosomes in the GnomAD database, including 11,567 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 0.14 (1899 hom., cov: 31)
  • Exomes 𝑓: 0.17 (9668 hom.)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.364+143G>A		intron_variant	Intron 4 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.364+143G>A		intron_variant	Intron 4 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21867 AN: 151810 Hom.: 1899 Cov.: 31

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.172 AC: 101661 AN: 592436 Hom.: 9668 AF XY: 0.171 AC XY: 54683 AN XY: 319388

African (AFR) AF: 0.0710 AC: 1142 AN: 16090

American (AMR) AF: 0.217 AC: 7611 AN: 35016

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 2559 AN: 19206

East Asian (EAS) AF: 0.329 AC: 11155 AN: 33956

South Asian (SAS) AF: 0.179 AC: 10994 AN: 61432

European-Finnish (FIN) AF: 0.136 AC: 5109 AN: 37486

Middle Eastern (MID) AF: 0.130 AC: 317 AN: 2434

European-Non Finnish (NFE) AF: 0.162 AC: 57538 AN: 355046

Other (OTH) AF: 0.165 AC: 5236 AN: 31770

GnomAD4 genome AF: 0.144 AC: 21867 AN: 151930 Hom.: 1899 Cov.: 31 AF XY: 0.144 AC XY: 10690 AN XY: 74262

African (AFR) AF: 0.0701 AC: 2904 AN: 41426

American (AMR) AF: 0.196 AC: 2991 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1665 AN: 5156

South Asian (SAS) AF: 0.187 AC: 900 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1277 AN: 10522

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

European-Non Finnish (NFE) AF: 0.163 AC: 11084 AN: 67950

Other (OTH) AF: 0.167 AC: 352 AN: 2108

Alfa AF: 0.156 Hom.: 4088

Bravo AF: 0.147

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.56
PhyloP100		0.087
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: rs2201584; hg19: chr1-67787715;