NM_001346222.1:c.-33-11362T>C

Variant names:

• chr22-37155567-A-G
• rs743777
• NM_001346222.1:c.-33-11362T>C

Variant summary

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

The NM_001346222.1(IL2RB):​c.-33-11362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,086 control chromosomes in the GnomAD database, including 10,117 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 0.35 (10117 hom., cov: 33)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 56 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	NM_001346222.1		c.-33-11362T>C		intron	N/A	NP_001333151.1
	IL2RB	NM_001346223.2		c.-33-11362T>C		intron	N/A	NP_001333152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	ENST00000429622.6	TSL:4	c.-33-11362T>C		intron	N/A	ENSP00000402685.2
	IL2RB	ENST00000445595.2	TSL:4	c.-34+6226T>C		intron	N/A	ENSP00000401020.2
	IL2RB	ENST00000453962.6	TSL:4	c.-33-11362T>C		intron	N/A	ENSP00000403731.2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53164 AN: 151968 Hom.: 10098 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.350 AC: 53228 AN: 152086 Hom.: 10117 Cov.: 33 AF XY: 0.344 AC XY: 25556 AN XY: 74354

African (AFR) AF: 0.501 AC: 20762 AN: 41444

American (AMR) AF: 0.253 AC: 3865 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3468

East Asian (EAS) AF: 0.121 AC: 626 AN: 5170

South Asian (SAS) AF: 0.168 AC: 811 AN: 4824

European-Finnish (FIN) AF: 0.332 AC: 3512 AN: 10584

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21540 AN: 67982

Other (OTH) AF: 0.322 AC: 681 AN: 2114

Alfa AF: 0.322 Hom.: 27872

Bravo AF: 0.355

Asia WGS AF: 0.182 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.83
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs743777; hg19: chr22-37551607;