chr22-37164552-C-T

Variant names:

• chr22-37164552-C-T
• rs229492
• NM_001346222.1:c.-34+10442G>A

Variant summary

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

The NM_001346222.1(IL2RB):​c.-34+10442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,864 control chromosomes in the GnomAD database, including 3,328 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 0.20 (3328 hom., cov: 30)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_001346222.1	c.-34+10442G>A		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-34+10406G>A		intron_variant	Intron 1 of 9		NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000429622.6	c.-34+10406G>A		intron_variant	Intron 1 of 9	4		ENSP00000402685.2
IL2RB	ENST00000445595.2	c.-224-2569G>A		intron_variant	Intron 1 of 10	4		ENSP00000401020.2
IL2RB	ENST00000453962.6	c.-34+10442G>A		intron_variant	Intron 1 of 9	4		ENSP00000403731.2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30208 AN: 151750 Hom.: 3318 Cov.: 30

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.199 AC: 30254 AN: 151864 Hom.: 3328 Cov.: 30 AF XY: 0.198 AC XY: 14697 AN XY: 74214

African (AFR) AF: 0.281 AC: 11607 AN: 41354

American (AMR) AF: 0.150 AC: 2294 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3472

East Asian (EAS) AF: 0.0957 AC: 495 AN: 5170

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4822

European-Finnish (FIN) AF: 0.184 AC: 1943 AN: 10542

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11570 AN: 67944

Other (OTH) AF: 0.198 AC: 416 AN: 2104

Alfa AF: 0.192 Hom.: 2109

Bravo AF: 0.195

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs229492; hg19: chr22-37560592;