rs2284033

Variant names:

• chr22-37137994-G-A
• rs2284033
• NM_000878.5:c.389-259C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37137994-G-A
• chr22-37137994-G-C

Variant summary

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

The NM_000878.5(IL2RB):​c.389-259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,852 control chromosomes in the GnomAD database, including 14,274 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 0.43 (14274 hom., cov: 31)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 92 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 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.389-259C>T		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.389-259C>T		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.389-259C>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.389-259C>T		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.407-259C>T		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.389-259C>T		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65305 AN: 151734 Hom.: 14269 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.430 AC: 65336 AN: 151852 Hom.: 14274 Cov.: 31 AF XY: 0.438 AC XY: 32498 AN XY: 74192

African (AFR) AF: 0.399 AC: 16517 AN: 41366

American (AMR) AF: 0.416 AC: 6345 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1371 AN: 3464

East Asian (EAS) AF: 0.590 AC: 3046 AN: 5164

South Asian (SAS) AF: 0.382 AC: 1830 AN: 4796

European-Finnish (FIN) AF: 0.540 AC: 5691 AN: 10546

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29202 AN: 67942

Other (OTH) AF: 0.387 AC: 815 AN: 2106

Alfa AF: 0.424 Hom.: 62648

Bravo AF: 0.421

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.40
PhyloP100		-2.4
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: rs2284033; hg19: chr22-37534034;