rs9622555

Variant names:

• chr22-37159545-G-T
• rs9622555
• NM_001346222.1:c.-33-15340C>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.-33-15340C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,998 control chromosomes in the GnomAD database, including 3,972 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 (3972 hom., cov: 32)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_001346222.1	c.-33-15340C>A		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-15340C>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.-33-15340C>A		intron_variant	Intron 1 of 9	4		ENSP00000402685.2
IL2RB	ENST00000445595.2	c.-34+2248C>A		intron_variant	Intron 2 of 10	4		ENSP00000401020.2
IL2RB	ENST00000453962.6	c.-33-15340C>A		intron_variant	Intron 1 of 9	4		ENSP00000403731.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33157 AN: 151880 Hom.: 3977 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.218 AC: 33163 AN: 151998 Hom.: 3972 Cov.: 32 AF XY: 0.215 AC XY: 15955 AN XY: 74290

African (AFR) AF: 0.121 AC: 5026 AN: 41442

American (AMR) AF: 0.196 AC: 3000 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3470

East Asian (EAS) AF: 0.104 AC: 540 AN: 5182

South Asian (SAS) AF: 0.161 AC: 775 AN: 4818

European-Finnish (FIN) AF: 0.264 AC: 2782 AN: 10530

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19283 AN: 67966

Other (OTH) AF: 0.223 AC: 472 AN: 2116

Alfa AF: 0.268 Hom.: 9599

Bravo AF: 0.212

Asia WGS AF: 0.116 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs9622555; hg19: chr22-37555585;