22-37132058-C-T

Variant names:

• chr22-37132058-C-T
• rs3218322
• NM_000878.5:c.903+326G>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.903+326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,994 control chromosomes in the GnomAD database, including 6,203 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 0.27 (6203 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 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.903+326G>A		intron	N/A	NP_000869.1
	IL2RB	NM_001346222.1		c.903+326G>A		intron	N/A	NP_001333151.1
	IL2RB	NM_001346223.2		c.903+326G>A		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.903+326G>A		intron	N/A	ENSP00000216223.5
	IL2RB	ENST00000698894.2		c.921+326G>A		intron	N/A	ENSP00000514013.1
	IL2RB	ENST00000429622.6	TSL:4	c.903+326G>A		intron	N/A	ENSP00000402685.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40483 AN: 151876 Hom.: 6210 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.266 AC: 40463 AN: 151994 Hom.: 6203 Cov.: 32 AF XY: 0.271 AC XY: 20148 AN XY: 74294

African (AFR) AF: 0.142 AC: 5892 AN: 41462

American (AMR) AF: 0.228 AC: 3481 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 879 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3079 AN: 5154

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4814

European-Finnish (FIN) AF: 0.301 AC: 3182 AN: 10556

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20953 AN: 67958

Other (OTH) AF: 0.272 AC: 575 AN: 2114

Alfa AF: 0.287 Hom.: 7505

Bravo AF: 0.254

Asia WGS AF: 0.457 AC: 1588 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	4.6
DANN	Benign	0.65
PhyloP100		1.2
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: rs3218322; hg19: chr22-37528098;