rs3218258

Variant names:

• chr22-37148205-G-A
• rs3218258
• NM_000878.5:c.-34+1620C>T

Variant summary

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

The NM_000878.5(IL2RB):​c.-34+1620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 150,120 control chromosomes in the GnomAD database, including 3,884 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 0.22 (3884 hom., cov: 33)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 22 publications found

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]

IL2RB Gene-Disease associations (from GenCC):

• immunodeficiency 63 with lymphoproliferation and autoimmunity

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

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 (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000878.5. 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
	IL2RB	NM_000878.5	MANE Select	c.-34+1620C>T		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.-33-4000C>T		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.-33-4000C>T		intron	N/A	NP_001333152.1	P14784

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	ENST00000216223.10	TSL:1 MANE Select	c.-34+1620C>T		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.-34+1620C>T		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.-33-4000C>T		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33067 AN: 150014 Hom.: 3890 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.220 AC: 33073 AN: 150120 Hom.: 3884 Cov.: 33 AF XY: 0.220 AC XY: 16150 AN XY: 73382

African (AFR) AF: 0.148 AC: 5871 AN: 39542

American (AMR) AF: 0.179 AC: 2723 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3466

East Asian (EAS) AF: 0.106 AC: 552 AN: 5190

South Asian (SAS) AF: 0.149 AC: 718 AN: 4828

European-Finnish (FIN) AF: 0.332 AC: 3510 AN: 10584

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18061 AN: 67966

Other (OTH) AF: 0.211 AC: 443 AN: 2096

Alfa AF: 0.244 Hom.: 7489

Bravo AF: 0.206

Asia WGS AF: 0.135 AC: 471 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	0.40
DANN	Benign	0.77
PhyloP100		-2.6
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: rs3218258; hg19: chr22-37544245;