Genetic Variant IL2RB:c.*415G>C (chr22-37127681-C-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.*415G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 157,788 control chromosomes in the GnomAD database, including 10,966 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 0.36 ( 10674 hom., cov: 31)

Exomes 𝑓: 0.29 ( 292 hom. )

Consequence

IL2RB
NM_000878.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0510

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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5 link	c.*415G>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000216223.10	NP_000869.1	P14784
IL2RB	NM_001346222.1 link	c.*415G>C	3_prime_UTR_variant	Exon 10 of 10		NP_001333151.1	P14784
IL2RB	NM_001346223.2 link	c.*415G>C	3_prime_UTR_variant	Exon 10 of 10		NP_001333152.1	P14784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10 link	c.*415G>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_000878.5	ENSP00000216223.5		P14784

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54661

AN:

151312

Hom.:

10646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.331

GnomAD4 exome

AF:

0.288

AC:

1831

AN:

6358

Hom.:

292

Cov.:

AF XY:

0.289

AC XY:

942

AN XY:

3262

show subpopulations

African (AFR)

AF:

0.496

AC:

131

AN:

264

American (AMR)

AF:

0.392

AC:

AN:

176

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

AN:

236

East Asian (EAS)

AF:

0.327

AC:

AN:

278

South Asian (SAS)

AF:

0.217

AC:

AN:

106

European-Finnish (FIN)

AF:

0.275

AC:

105

AN:

382

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.269

AC:

1185

AN:

4404

Other (OTH)

AF:

0.310

AC:

139

AN:

448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.361

AC:

54735

AN:

151430

Hom.:

10674

Cov.:

AF XY:

0.362

AC XY:

26765

AN XY:

73962

show subpopulations

African (AFR)

AF:

0.512

AC:

21105

AN:

41246

American (AMR)

AF:

0.361

AC:

5509

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1165

AN:

3466

East Asian (EAS)

AF:

0.340

AC:

1736

AN:

5112

South Asian (SAS)

AF:

0.269

AC:

1290

AN:

4794

European-Finnish (FIN)

AF:

0.288

AC:

3012

AN:

10450

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19790

AN:

67818

Other (OTH)

AF:

0.328

AC:

688

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1705

3410

5115

6820

8525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.278

Hom.:

3402

Bravo

AF:

0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

(source)

DANN

Benign

0.47

PhyloP100

0.051

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over