rs3218295

Variant names:

• chr22-37137028-C-T
• rs3218295
• NM_000878.5:c.537+559G>A

Variant summary

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

The NM_000878.5(IL2RB):​c.537+559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,022 control chromosomes in the GnomAD database, including 3,940 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 0.21 (3940 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 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.537+559G>A		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.537+559G>A		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.537+559G>A		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.537+559G>A		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.555+559G>A		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.537+559G>A		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31135 AN: 151904 Hom.: 3938 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.205 AC: 31172 AN: 152022 Hom.: 3940 Cov.: 32 AF XY: 0.211 AC XY: 15644 AN XY: 74294

African (AFR) AF: 0.347 AC: 14401 AN: 41442

American (AMR) AF: 0.0978 AC: 1495 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3468

East Asian (EAS) AF: 0.167 AC: 863 AN: 5160

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4822

European-Finnish (FIN) AF: 0.256 AC: 2701 AN: 10552

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9593 AN: 67976

Other (OTH) AF: 0.163 AC: 345 AN: 2114

Alfa AF: 0.157 Hom.: 9268

Bravo AF: 0.197

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		-0.42
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: rs3218295; hg19: chr22-37533068;