22-37123824-T-C

Variant names:

• chr22-37123824-T-C
• rs5995385
• ENST00000703410.1:c.904-4666A>G

Variant summary

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

The ENST00000703410.1(IL2RB):​c.904-4666A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,990 control chromosomes in the GnomAD database, including 16,814 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 0.46 (16814 hom., cov: 31)
• Consequence: IL2RB ENST00000703410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 10 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000703410.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	ENST00000703410.1		c.904-4666A>G		intron	N/A	ENSP00000516411.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70244 AN: 151872 Hom.: 16789 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.463 AC: 70319 AN: 151990 Hom.: 16814 Cov.: 31 AF XY: 0.466 AC XY: 34609 AN XY: 74296

African (AFR) AF: 0.369 AC: 15277 AN: 41444

American (AMR) AF: 0.389 AC: 5947 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1552 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1970 AN: 5160

South Asian (SAS) AF: 0.586 AC: 2822 AN: 4814

European-Finnish (FIN) AF: 0.583 AC: 6157 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35188 AN: 67940

Other (OTH) AF: 0.450 AC: 949 AN: 2108

Alfa AF: 0.495 Hom.: 66122

Bravo AF: 0.438

Asia WGS AF: 0.532 AC: 1851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.3
DANN	Benign	0.42
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs5995385; hg19: chr22-37519864;