Genetic Variant IL2RB:c.203+433G>A (chr22-37143088-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.987

Publications

13 publications found

Variant links:

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)

IL2RB links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL2RB	NM_000878.5	MANE Select	c.203+433G>A	intron	N/A	NP_000869.1	P14784
IL2RB	NM_001346222.1		c.203+433G>A	intron	N/A	NP_001333151.1	P14784
IL2RB	NM_001346223.2		c.203+433G>A	intron	N/A	NP_001333152.1	P14784

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL2RB	ENST00000216223.10	TSL:1 MANE Select	c.203+433G>A	intron	N/A	ENSP00000216223.5	P14784
IL2RB	ENST00000698894.2		c.203+433G>A	intron	N/A	ENSP00000514013.1	A0A8V8TMD3
IL2RB	ENST00000429622.6	TSL:4	c.203+433G>A	intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47641

AN:

151818

Hom.:

7659

Cov.:

show subpopulations

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.:

AF XY:

0.315

AC XY:

23383

AN XY:

74256

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18959

AN:

67942

Other (OTH)

AF:

0.269

AC:

567

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1614

3227

4841

6454

8068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.38

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over