22-37143088-C-T

Variant names:

• chr22-37143088-C-T
• rs1003694
• NM_000878.5:c.203+433G>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.203+433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,936 control chromosomes in the GnomAD database, including 7,663 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 0.31 (7663 hom., cov: 31)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 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.203+433G>A		intron	N/A	NP_000869.1
	IL2RB	NM_001346222.1		c.203+433G>A		intron	N/A	NP_001333151.1
	IL2RB	NM_001346223.2		c.203+433G>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.203+433G>A		intron	N/A	ENSP00000216223.5
	IL2RB	ENST00000698894.2		c.203+433G>A		intron	N/A	ENSP00000514013.1
	IL2RB	ENST00000429622.6	TSL:4	c.203+433G>A		intron	N/A	ENSP00000402685.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47641 AN: 151818 Hom.: 7659 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.314 AC: 47663 AN: 151936 Hom.: 7663 Cov.: 31 AF XY: 0.315 AC XY: 23383 AN XY: 74256

African (AFR) AF: 0.382 AC: 15822 AN: 41430

American (AMR) AF: 0.323 AC: 4942 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1909 AN: 5134

South Asian (SAS) AF: 0.256 AC: 1230 AN: 4808

European-Finnish (FIN) AF: 0.277 AC: 2927 AN: 10550

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18959 AN: 67942

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.286 Hom.: 21450

Bravo AF: 0.324

Asia WGS AF: 0.296 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.38
PhyloP100		-0.99
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: rs1003694; hg19: chr22-37539128;