rs228973

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 HGVSp Effect #exon/exons MANE UniProt
IL2RBNM_000878.5 linkuse as main transcriptc.-33-1567T>C intron_variant ENST00000216223.10
IL2RBNM_001346222.1 linkuse as main transcriptc.-33-1567T>C intron_variant
IL2RBNM_001346223.2 linkuse as main transcriptc.-33-1567T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL2RBENST00000216223.10 linkuse as main transcriptc.-33-1567T>C intron_variant 1 NM_000878.5 P4

Frequencies

GnomAD3 genomes
AF:
0.347
AC:
52633
AN:
151464
Hom.:
9320
Cov.:
30
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.:
30
AF XY:
0.351
AC XY:
25957
AN XY:
74040
show subpopulations
Gnomad4 AFR
AF:
0.337
Gnomad4 AMR
AF:
0.425
Gnomad4 ASJ
AF:
0.323
Gnomad4 EAS
AF:
0.483
Gnomad4 SAS
AF:
0.272
Gnomad4 FIN
AF:
0.365
Gnomad4 NFE
AF:
0.328
Gnomad4 OTH
AF:
0.332
Alfa
AF:
0.336
Hom.:
10602
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
DANN
Benign
0.28

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.

Other links and lift over

dbSNP: rs228973; hg19: chr22-37541812; API