rs2051582

Positions:

• chr22-37162316-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346222.1(IL2RB):​c.-34+12678C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,026 control chromosomes in the GnomAD database, including 2,513 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 0.18 (2513 hom., cov: 31)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

Genes affected

IL2RB (HGNC:6009): (interleukin 2 receptor subunit beta) The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. The low affinity form is a monomer of the alpha subunit and is not involved in signal transduction. The intermediate affinity form consists of an alpha/beta subunit heterodimer, while the high affinity form consists of an alpha/beta/gamma subunit heterotrimer. Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. The protein encoded by this gene represents the beta subunit and is a type I membrane protein. The use of alternative promoters results in multiple transcript variants encoding the same protein. The protein is primarily expressed in the hematopoietic system. The use by some variants of an alternate promoter in an upstream long terminal repeat (LTR) results in placenta-specific expression. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RB	NM_001346222.1	c.-34+12678C>T		intron_variant
IL2RB	NM_001346223.2	c.-34+12642C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RB	ENST00000429622.6	c.-34+12642C>T		intron_variant		4		P4
IL2RB	ENST00000445595.2	c.-224-333C>T		intron_variant		4		P4
IL2RB	ENST00000453962.6	c.-34+12678C>T		intron_variant		4		P4

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26991 AN: 151908 Hom.: 2515 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.178 AC: 27009 AN: 152026 Hom.: 2513 Cov.: 31 AF XY: 0.176 AC XY: 13103 AN XY: 74322

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.182

Alfa AF: 0.207 Hom.: 4830

Bravo AF: 0.171

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2051582; hg19: chr22-37558356;