rs228942

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000878.5(IL2RB):c.1173C>A(p.Asp391Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,613,818 control chromosomes in the GnomAD database, including 26,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2482 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23988 hom. )

Consequence

IL2RB
NM_000878.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.49

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039142966).

BP6

Variant 22-37128579-G-T is Benign according to our data. Variant chr22-37128579-G-T is described in ClinVar as [Benign]. Clinvar id is 1164671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL2RB	NM_000878.5 linkuse as main transcript	c.1173C>A	p.Asp391Glu	missense_variant	10/10	ENST00000216223.10
IL2RB	NM_001346222.1 linkuse as main transcript	c.1173C>A	p.Asp391Glu	missense_variant	10/10
IL2RB	NM_001346223.2 linkuse as main transcript	c.1173C>A	p.Asp391Glu	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RB	ENST00000216223.10 linkuse as main transcript	c.1173C>A	p.Asp391Glu	missense_variant	10/10	1	NM_000878.5	P4

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25569

AN:

152022

Hom.:

2480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.192

AC:

48194

AN:

251134

Hom.:

5107

AF XY:

0.187

AC XY:

25365

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.0916

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.265

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.178

AC:

259785

AN:

1461678

Hom.:

23988

Cov.:

AF XY:

0.176

AC XY:

128079

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0906

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.168

AC:

25568

AN:

152140

Hom.:

2482

Cov.:

AF XY:

0.171

AC XY:

12744

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0953

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.177

Hom.:

5853

Bravo

AF:

0.171

TwinsUK

AF:

0.180

AC:

667

ALSPAC

AF:

0.186

AC:

715

ESP6500AA

AF:

0.0921

AC:

406

ESP6500EA

AF:

0.184

AC:

1585

ExAC

AF:

0.185

AC:

22419

Asia WGS

AF:

0.169

AC:

590

AN:

3478

EpiCase

AF:

0.170

EpiControl

AF:

0.170

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

IL2RB-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

Cadd

Benign

0.0080

Dann

Benign

0.20

DEOGEN2

Benign

0.29

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.13

REVEL

Benign

0.071

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.011

MutPred

0.15

Gain of glycosylation at P386 (P = 0.1426);

MPC

0.079

ClinPred

0.00030

GERP RS

2.2

Varity_R

0.036

gMVP

0.054

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over