Genetic Variant IL2RB:c.-34+934A>C (chr22-37148891-T-G) – 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.-34+934A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 151,976 control chromosomes in the GnomAD database, including 48,086 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 0.79 ( 48086 hom., cov: 30)

Consequence

IL2RB
NM_000878.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.647

Publications

12 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5 link	c.-34+934A>C	intron_variant	Intron 1 of 9	ENST00000216223.10	NP_000869.1	P14784
IL2RB	NM_001346222.1 link	c.-33-4686A>C	intron_variant	Intron 1 of 9		NP_001333151.1	P14784
IL2RB	NM_001346223.2 link	c.-33-4686A>C	intron_variant	Intron 1 of 9		NP_001333152.1	P14784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10 link	c.-34+934A>C		intron_variant	Intron 1 of 9	1	NM_000878.5	ENSP00000216223.5		P14784

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

120048

AN:

151858

Hom.:

48027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

0.920

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.720

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.769

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

GnomAD4 genome

AF:

0.791

AC:

120165

AN:

151976

Hom.:

48086

Cov.:

AF XY:

0.790

AC XY:

58682

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.929

AC:

38497

AN:

41458

American (AMR)

AF:

0.761

AC:

11615

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

2743

AN:

3472

East Asian (EAS)

AF:

0.721

AC:

3716

AN:

5154

South Asian (SAS)

AF:

0.751

AC:

3616

AN:

4814

European-Finnish (FIN)

AF:

0.764

AC:

8079

AN:

10576

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.724

AC:

49199

AN:

67924

Other (OTH)

AF:

0.770

AC:

1625

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1235

2470

3705

4940

6175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.749

Hom.:

135402

Bravo

AF:

0.797

Asia WGS

AF:

0.740

AC:

2578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.71

(source)

DANN

Benign

0.38

PhyloP100

-0.65

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over