NM_000878.5:c.750C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000878.5(IL2RB):c.750C>T(p.Gly250Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,612,546 control chromosomes in the GnomAD database, including 151,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G250G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.43 ( 14137 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136966 hom. )

Consequence

IL2RB
NM_000878.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.458

Publications

43 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 Submitted by: Labcorp Genetics (formerly Invitae)

IL2RB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.045).

BP6

Variant 22-37135396-G-A is Benign according to our data. Variant chr22-37135396-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5 link	c.750C>T	p.Gly250Gly	synonymous_variant	Exon 8 of 10	ENST00000216223.10	NP_000869.1	P14784
IL2RB	NM_001346222.1 link	c.750C>T	p.Gly250Gly	synonymous_variant	Exon 8 of 10		NP_001333151.1	P14784
IL2RB	NM_001346223.2 link	c.750C>T	p.Gly250Gly	synonymous_variant	Exon 8 of 10		NP_001333152.1	P14784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10 link	c.750C>T	p.Gly250Gly	synonymous_variant	Exon 8 of 10	1	NM_000878.5	ENSP00000216223.5		P14784

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65222

AN:

151830

Hom.:

14127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.394

GnomAD2 exomes

AF:

0.423

AC:

106366

AN:

251204

AF XY:

0.422

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.412

GnomAD4 exome

AF:

0.432

AC:

630484

AN:

1460598

Hom.:

136966

Cov.:

AF XY:

0.429

AC XY:

311952

AN XY:

726732

show subpopulations

African (AFR)

AF:

0.405

AC:

13559

AN:

33464

American (AMR)

AF:

0.403

AC:

18033

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

9896

AN:

26106

East Asian (EAS)

AF:

0.440

AC:

17465

AN:

39668

South Asian (SAS)

AF:

0.372

AC:

32065

AN:

86216

European-Finnish (FIN)

AF:

0.517

AC:

27608

AN:

53386

Middle Eastern (MID)

AF:

0.304

AC:

1751

AN:

5762

European-Non Finnish (NFE)

AF:

0.437

AC:

485097

AN:

1110942

Other (OTH)

AF:

0.414

AC:

25010

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

17104

34208

51311

68415

85519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14770

29540

44310

59080

73850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.430

AC:

65271

AN:

151948

Hom.:

14137

Cov.:

AF XY:

0.436

AC XY:

32390

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.412

AC:

17080

AN:

41422

American (AMR)

AF:

0.420

AC:

6426

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1346

AN:

3468

East Asian (EAS)

AF:

0.420

AC:

2171

AN:

5164

South Asian (SAS)

AF:

0.371

AC:

1787

AN:

4820

European-Finnish (FIN)

AF:

0.534

AC:

5641

AN:

10562

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.434

AC:

29475

AN:

67918

Other (OTH)

AF:

0.389

AC:

820

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1928

3855

5783

7710

9638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.423

Hom.:

25869

Bravo

AF:

0.422

Asia WGS

AF:

0.407

AC:

1414

AN:

3478

EpiCase

AF:

0.417

EpiControl

AF:

0.416

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -

IL2RB-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Immunodeficiency 63 with lymphoproliferation and autoimmunity

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.4

(source)

DANN

Benign

0.64

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over