chr22-37146722-G-A

Variant names:

• chr22-37146722-G-A
• rs2284034
• NM_000878.5:c.-33-2517C>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.-33-2517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,088 control chromosomes in the GnomAD database, including 7,007 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 0.29 (7007 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 10 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 Submitted by: 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 = 0.432 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	NM_000878.5	MANE Select	c.-33-2517C>T		intron	N/A	NP_000869.1
	IL2RB	NM_001346222.1		c.-33-2517C>T		intron	N/A	NP_001333151.1
	IL2RB	NM_001346223.2		c.-33-2517C>T		intron	N/A	NP_001333152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	ENST00000216223.10	TSL:1 MANE Select	c.-33-2517C>T		intron	N/A	ENSP00000216223.5
	IL2RB	ENST00000698890.1		c.-305C>T		5_prime_UTR	Exon 1 of 10	ENSP00000514009.1
	IL2RB	ENST00000698894.2		c.-33-2517C>T		intron	N/A	ENSP00000514013.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44186 AN: 151970 Hom.: 7006 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.291 AC: 44194 AN: 152088 Hom.: 7007 Cov.: 32 AF XY: 0.294 AC XY: 21869 AN XY: 74320

African (AFR) AF: 0.172 AC: 7136 AN: 41486

American (AMR) AF: 0.393 AC: 6013 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1102 AN: 3472

East Asian (EAS) AF: 0.448 AC: 2307 AN: 5154

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4824

European-Finnish (FIN) AF: 0.360 AC: 3804 AN: 10564

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21570 AN: 67972

Other (OTH) AF: 0.292 AC: 618 AN: 2114

Alfa AF: 0.316 Hom.: 10800

Bravo AF: 0.297

Asia WGS AF: 0.290 AC: 1011 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	0.069
DANN	Benign	0.45
PhyloP100		-3.0
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: rs2284034; hg19: chr22-37542762;