rs228973

Positions:

• chr22-37145772-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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]

ACMG classification

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
IL2RB	NM_000878.5	c.-33-1567T>C		intron_variant		ENST00000216223.10
IL2RB	NM_001346222.1	c.-33-1567T>C		intron_variant
IL2RB	NM_001346223.2	c.-33-1567T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RB	ENST00000216223.10	c.-33-1567T>C		intron_variant		1	NM_000878.5	P4

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52633 AN: 151464 Hom.: 9320 Cov.: 30

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

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

Other links and lift over

dbSNP: rs228973; hg19: chr22-37541812;