chr22-37138907-G-A

Variant names:

• chr22-37138907-G-A
• rs228960
• NM_000878.5:c.388+210C>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.388+210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,886 control chromosomes in the GnomAD database, including 18,827 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 0.49 (18827 hom., cov: 31)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 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.388+210C>T		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.388+210C>T		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.388+210C>T		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.388+210C>T		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.406+210C>T		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.388+210C>T		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73925 AN: 151766 Hom.: 18800 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.487 AC: 73993 AN: 151886 Hom.: 18827 Cov.: 31 AF XY: 0.490 AC XY: 36391 AN XY: 74244

African (AFR) AF: 0.629 AC: 26044 AN: 41394

American (AMR) AF: 0.431 AC: 6587 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1369 AN: 3472

East Asian (EAS) AF: 0.597 AC: 3083 AN: 5164

South Asian (SAS) AF: 0.392 AC: 1884 AN: 4806

European-Finnish (FIN) AF: 0.477 AC: 5041 AN: 10572

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28573 AN: 67896

Other (OTH) AF: 0.420 AC: 885 AN: 2108

Alfa AF: 0.460 Hom.: 2469

Bravo AF: 0.492

Asia WGS AF: 0.494 AC: 1715 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.73
PhyloP100		-1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs228960;

hg19: chr22-37534947;