rs3218339

Variant names:

• chr22-37125171-C-T
• rs3218339
• ENST00000703410.1:c.904-6013G>A

Variant summary

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

The ENST00000703410.1(IL2RB):​c.904-6013G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,210 control chromosomes in the GnomAD database, including 882 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 0.11 (882 hom., cov: 30)
• Consequence: IL2RB ENST00000703410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 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.904-6013G>A		intron_variant	Intron 9 of 9			ENSP00000516411.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16157 AN: 152092 Hom.: 880 Cov.: 30

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.106 AC: 16175 AN: 152210 Hom.: 882 Cov.: 30 AF XY: 0.107 AC XY: 7942 AN XY: 74416

African (AFR) AF: 0.0712 AC: 2960 AN: 41544

American (AMR) AF: 0.0828 AC: 1266 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.140 AC: 722 AN: 5168

South Asian (SAS) AF: 0.124 AC: 595 AN: 4816

European-Finnish (FIN) AF: 0.107 AC: 1131 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8618 AN: 68002

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.124 Hom.: 1584

Bravo AF: 0.104

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.97

Splicing

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

Other links and lift over

dbSNP: rs3218339; hg19: chr22-37521211;