rs3218339

Positions:

• chr22-37125171-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.37125171C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000703410.1	c.904-6013G>A		intron_variant				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

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.0828

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.107

Alfa AF: 0.125 Hom.: 787

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218339; hg19: chr22-37521211;