chr22-37141474-T-C

Variant names:

• chr22-37141474-T-C
• rs228966
• NM_000878.5:c.282+960A>G

Variant summary

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

The NM_000878.5(IL2RB):​c.282+960A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,880 control chromosomes in the GnomAD database, including 20,793 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 0.51 (20793 hom., cov: 31)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 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.282+960A>G		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.282+960A>G		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.282+960A>G		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.282+960A>G		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.300+960A>G		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.282+960A>G		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77450 AN: 151760 Hom.: 20766 Cov.: 31

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.510 AC: 77518 AN: 151880 Hom.: 20793 Cov.: 31 AF XY: 0.513 AC XY: 38085 AN XY: 74208

African (AFR) AF: 0.676 AC: 28008 AN: 41430

American (AMR) AF: 0.454 AC: 6935 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3464

East Asian (EAS) AF: 0.629 AC: 3232 AN: 5142

South Asian (SAS) AF: 0.448 AC: 2161 AN: 4820

European-Finnish (FIN) AF: 0.479 AC: 5046 AN: 10528

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29302 AN: 67908

Other (OTH) AF: 0.443 AC: 932 AN: 2104

Alfa AF: 0.465 Hom.: 9203

Bravo AF: 0.517

Asia WGS AF: 0.531 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.40
PhyloP100		0.062
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: rs228966; hg19: chr22-37537514;