Genetic Variant IL2RB:c.-33-1567T>C (chr22-37145772-A-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.-33-1567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,582 control chromosomes in the GnomAD database, including 9,332 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 0.35 ( 9332 hom., cov: 30)

Consequence

IL2RB
NM_000878.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5 link	c.-33-1567T>C	intron_variant	Intron 1 of 9	ENST00000216223.10	NP_000869.1	P14784
IL2RB	NM_001346222.1 link	c.-33-1567T>C	intron_variant	Intron 1 of 9		NP_001333151.1	P14784
IL2RB	NM_001346223.2 link	c.-33-1567T>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.-33-1567T>C		intron_variant	Intron 1 of 9	1	NM_000878.5	ENSP00000216223.5		P14784

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52633

AN:

151464

Hom.:

9320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.335

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

GnomAD4 genome

AF:

0.347

AC:

52673

AN:

151582

Hom.:

9332

Cov.:

AF XY:

0.351

AC XY:

25957

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.337

AC:

13932

AN:

41332

American (AMR)

AF:

0.425

AC:

6495

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1119

AN:

3468

East Asian (EAS)

AF:

0.483

AC:

2462

AN:

5098

South Asian (SAS)

AF:

0.272

AC:

1304

AN:

4790

European-Finnish (FIN)

AF:

0.365

AC:

3840

AN:

10512

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.328

AC:

22261

AN:

67802

Other (OTH)

AF:

0.332

AC:

700

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1674

3348

5021

6695

8369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.337

Hom.:

19299

Bravo

AF:

0.361

Asia WGS

AF:

0.337

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

(source)

DANN

Benign

0.28

PhyloP100

-0.13

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