dbSNP rs228960: IL2RB:c.388+210C>T (chr22-37138907-G-A) – 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.388+210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,886 control chromosomes in the GnomAD database, including 18,827 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 0.49 ( 18827 hom., cov: 31)

Consequence

IL2RB
NM_000878.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

6 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5 link	c.388+210C>T	intron_variant	Intron 5 of 9	ENST00000216223.10	NP_000869.1	P14784
IL2RB	NM_001346222.1 link	c.388+210C>T	intron_variant	Intron 5 of 9		NP_001333151.1	P14784
IL2RB	NM_001346223.2 link	c.388+210C>T	intron_variant	Intron 5 of 9		NP_001333152.1	P14784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10 link	c.388+210C>T		intron_variant	Intron 5 of 9	1	NM_000878.5	ENSP00000216223.5		P14784

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73925

AN:

151766

Hom.:

18800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.596

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.425

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

GnomAD4 genome

AF:

0.487

AC:

73993

AN:

151886

Hom.:

18827

Cov.:

AF XY:

0.490

AC XY:

36391

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.629

AC:

26044

AN:

41394

American (AMR)

AF:

0.431

AC:

6587

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1369

AN:

3472

East Asian (EAS)

AF:

0.597

AC:

3083

AN:

5164

South Asian (SAS)

AF:

0.392

AC:

1884

AN:

4806

European-Finnish (FIN)

AF:

0.477

AC:

5041

AN:

10572

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28573

AN:

67896

Other (OTH)

AF:

0.420

AC:

885

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1856

3712

5569

7425

9281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.460

Hom.:

2469

Bravo

AF:

0.492

Asia WGS

AF:

0.494

AC:

1715

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.21

(source)

DANN

Benign

0.73

PhyloP100

-1.1

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