rs3218266

Variant names:

• chr22-37145791-G-C
• rs3218266
• NM_000878.5:c.-33-1586C>G

Variant summary

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

The NM_000878.5(IL2RB):​c.-33-1586C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,790 control chromosomes in the GnomAD database, including 7,300 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 0.29 (7300 hom., cov: 30)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5	c.-33-1586C>G		intron_variant	Intron 1 of 9	ENST00000216223.10	NP_000869.1
IL2RB	NM_001346222.1	c.-33-1586C>G		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-1586C>G		intron_variant	Intron 1 of 9		NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10	c.-33-1586C>G		intron_variant	Intron 1 of 9	1	NM_000878.5	ENSP00000216223.5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44669 AN: 151672 Hom.: 7301 Cov.: 30

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.294 AC: 44662 AN: 151790 Hom.: 7300 Cov.: 30 AF XY: 0.299 AC XY: 22162 AN XY: 74140

African (AFR) AF: 0.153 AC: 6358 AN: 41426

American (AMR) AF: 0.403 AC: 6157 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2465 AN: 5126

South Asian (SAS) AF: 0.272 AC: 1306 AN: 4806

European-Finnish (FIN) AF: 0.365 AC: 3839 AN: 10522

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22233 AN: 67854

Other (OTH) AF: 0.296 AC: 625 AN: 2108

Alfa AF: 0.309 Hom.: 1075

Bravo AF: 0.299

Asia WGS AF: 0.323 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3218266; hg19: chr22-37541831;