rs228975

Variant names:

• chr22-37146161-G-A
• rs228975
• NM_000878.5:c.-33-1956C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37146161-G-A
• chr22-37146161-G-C
• chr22-37146161-G-T

Variant summary

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

The NM_000878.5(IL2RB):​c.-33-1956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,804 control chromosomes in the GnomAD database, including 13,008 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 0.41 (13008 hom., cov: 30)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5	c.-33-1956C>T		intron_variant	Intron 1 of 9	ENST00000216223.10	NP_000869.1
IL2RB	NM_001346222.1	c.-33-1956C>T		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-1956C>T		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.-33-1956C>T		intron_variant	Intron 1 of 9	1	NM_000878.5	ENSP00000216223.5

Frequencies

GnomAD3 genomes AF: 0.409 AC: 61978 AN: 151684 Hom.: 12998 Cov.: 30

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.409 AC: 62017 AN: 151804 Hom.: 13008 Cov.: 30 AF XY: 0.415 AC XY: 30758 AN XY: 74178

African (AFR) AF: 0.433 AC: 17929 AN: 41362

American (AMR) AF: 0.450 AC: 6859 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3611 AN: 5140

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4498 AN: 10530

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24705 AN: 67918

Other (OTH) AF: 0.377 AC: 796 AN: 2114

Alfa AF: 0.381 Hom.: 8716

Bravo AF: 0.420

Asia WGS AF: 0.478 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.57
PhyloP100		-0.38
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: rs228975; hg19: chr22-37542201;