Variant 22-37143673-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000878.5(IL2RB):c.89-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,431,338 control chromosomes in the GnomAD database, including 31,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 3144 hom., cov: 31)

Exomes 𝑓: 0.20 ( 27901 hom. )

Consequence

IL2RB
NM_000878.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.39

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:

IL2RB (HGNC:):

IL2RB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-37143673-T-C is Benign according to our data. Variant chr22-37143673-T-C is described in ClinVar as [Benign]. Clinvar id is 2688422.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
IL2RB	NM_000878.5 linkuse as main transcript	c.89-38A>G	intron_variant	ENST00000216223.10	NP_000869.1	P14784
IL2RB	NM_001346222.1 linkuse as main transcript	c.89-38A>G	intron_variant		NP_001333151.1	P14784
IL2RB	NM_001346223.2 linkuse as main transcript	c.89-38A>G	intron_variant		NP_001333152.1	P14784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10 linkuse as main transcript	c.89-38A>G		intron_variant		1	NM_000878.5	ENSP00000216223.5		P14784

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27867

AN:

151632

Hom.:

3141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0886

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.177

GnomAD3 exomes

AF:

0.221

AC:

55065

AN:

249204

Hom.:

7263

AF XY:

0.211

AC XY:

28513

AN XY:

134820

show subpopulations

Gnomad AFR exome

AF:

0.0847

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.439

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.199

AC:

254896

AN:

1279588

Hom.:

27901

Cov.:

AF XY:

0.195

AC XY:

126185

AN XY:

645822

show subpopulations

Gnomad4 AFR exome

AF:

0.0840

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.408

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.184

AC:

27872

AN:

151750

Hom.:

3144

Cov.:

AF XY:

0.189

AC XY:

14025

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.0885

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.434

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.188

Hom.:

4318

Bravo

AF:

0.183

Asia WGS

AF:

0.230

AC:

797

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.089

DANN

Benign

0.61

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