22-37172384-C-T

Variant names:

• chr22-37172384-C-T
• rs229501
• NM_001346222.1:c.-34+2610G>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+2610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 152,226 control chromosomes in the GnomAD database, including 817 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 0.056 (817 hom., cov: 32)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 1 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, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

IL2RB-AS1 (HGNC:40300):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346222.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	NM_001346222.1		c.-34+2610G>A		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.-34+2574G>A		intron	N/A	NP_001333152.1	P14784
	IL2RB-AS1	NR_199008.1		n.206+5420C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	ENST00000429622.6	TSL:4	c.-34+2574G>A		intron	N/A	ENSP00000402685.2	P14784
	IL2RB	ENST00000445595.2	TSL:4	c.-225+2574G>A		intron	N/A	ENSP00000401020.2	P14784
	IL2RB	ENST00000453962.6	TSL:4	c.-34+2610G>A		intron	N/A	ENSP00000403731.2	P14784

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8521 AN: 152108 Hom.: 819 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0561 AC: 8536 AN: 152226 Hom.: 817 Cov.: 32 AF XY: 0.0540 AC XY: 4022 AN XY: 74450

African (AFR) AF: 0.193 AC: 8017 AN: 41492

American (AMR) AF: 0.0209 AC: 320 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68016

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.00191 Hom.: 1

Bravo AF: 0.0649

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.55
DANN	Benign	0.66
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs229501; hg19: chr22-37568424;