rs3218253

Variant names:

• chr22-37148770-G-A
• rs3218253
• NM_000878.5:c.-34+1055C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37148770-G-A
• chr22-37148770-G-C
• chr22-37148770-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.-34+1055C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,004 control chromosomes in the GnomAD database, including 3,773 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 0.22 (3773 hom., cov: 31)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 45 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5	c.-34+1055C>T		intron_variant	Intron 1 of 9	ENST00000216223.10	NP_000869.1
IL2RB	NM_001346222.1	c.-33-4565C>T		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-4565C>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.-34+1055C>T		intron_variant	Intron 1 of 9	1	NM_000878.5	ENSP00000216223.5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32783 AN: 151886 Hom.: 3779 Cov.: 31

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.216 AC: 32789 AN: 152004 Hom.: 3773 Cov.: 31 AF XY: 0.214 AC XY: 15900 AN XY: 74300

African (AFR) AF: 0.142 AC: 5877 AN: 41486

American (AMR) AF: 0.179 AC: 2743 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3466

East Asian (EAS) AF: 0.105 AC: 543 AN: 5166

South Asian (SAS) AF: 0.149 AC: 715 AN: 4812

European-Finnish (FIN) AF: 0.302 AC: 3188 AN: 10556

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18045 AN: 67916

Other (OTH) AF: 0.213 AC: 450 AN: 2110

Alfa AF: 0.247 Hom.: 12590

Bravo AF: 0.207

Asia WGS AF: 0.135 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.77
PhyloP100		0.50
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: rs3218253; hg19: chr22-37544810;