rs84460

chr22-37129691-A-Gchr22-37129691-A-T

Variant summary

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

The NM_000878.5(IL2RB):c.904-843T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,120 control chromosomes in the GnomAD database, including 8,357 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 0.33 (8357 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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 (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RB	NM_000878.5	c.904-843T>C		intron_variant		ENST00000216223.10
IL2RB	NM_001346222.1	c.904-843T>C		intron_variant
IL2RB	NM_001346223.2	c.904-843T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RB	ENST00000216223.10	c.904-843T>C		intron_variant		1	NM_000878.5	P4

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49745 AN: 152002 Hom.: 8339 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.327 AC: 49800 AN: 152120 Hom.: 8357 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74348

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.300

Alfa AF: 0.301 Hom.: 9628

Bravo AF: 0.335

Asia WGS AF: 0.282 AC: 984 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	1.6
Dann	Benign	0.58

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: rs84460; hg19: chr22-37525731;