22-37129691-A-G

Variant names:

• chr22-37129691-A-G
• rs84460
• NM_000878.5:c.904-843T>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.904-843T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,120 control chromosomes in the GnomAD database, including 8,357 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 0.33 (8357 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589
• Publications: 12 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 (AFR) allele frequency at 95% confidence interval = 0.369 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.904-843T>C		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.904-843T>C		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.904-843T>C		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.904-843T>C		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.922-843T>C		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.904-843T>C		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49745 AN: 152002 Hom.: 8339 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.327 AC: 49800 AN: 152120 Hom.: 8357 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74348

African (AFR) AF: 0.374 AC: 15509 AN: 41484

American (AMR) AF: 0.356 AC: 5443 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1829 AN: 5178

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4828

European-Finnish (FIN) AF: 0.287 AC: 3040 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20386 AN: 67986

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.305 Hom.: 14410

Bravo AF: 0.335

Asia WGS AF: 0.282 AC: 984 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	1.6
DANN	Benign	0.58
PhyloP100		-0.59
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: rs84460; hg19: chr22-37525731;