ENST00000703410.1:c.904-5773C>A

Variant names:

• chr22-37124931-G-T
• rs228937
• ENST00000703410.1:c.904-5773C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000703410.1(IL2RB):​c.904-5773C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,990 control chromosomes in the GnomAD database, including 48,945 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 0.80 (48945 hom., cov: 29)
• Consequence: IL2RB ENST00000703410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 14 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000703410.1	c.904-5773C>A		intron_variant	Intron 9 of 9			ENSP00000516411.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121684 AN: 151872 Hom.: 48903 Cov.: 29

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.801 AC: 121785 AN: 151990 Hom.: 48945 Cov.: 29 AF XY: 0.803 AC XY: 59713 AN XY: 74318

African (AFR) AF: 0.791 AC: 32738 AN: 41412

American (AMR) AF: 0.834 AC: 12739 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2922 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3301 AN: 5146

South Asian (SAS) AF: 0.867 AC: 4178 AN: 4820

European-Finnish (FIN) AF: 0.838 AC: 8881 AN: 10592

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54414 AN: 67958

Other (OTH) AF: 0.796 AC: 1677 AN: 2108

Alfa AF: 0.789 Hom.: 23468

Bravo AF: 0.798

Asia WGS AF: 0.788 AC: 2743 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	2.5
DANN	Benign	0.57
PhyloP100		0.092

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs228937; hg19: chr22-37520971; COSMIC: COSV53427549;