NM_001346222.1:c.-33-14594G>C

Variant names:

• chr22-37158799-C-G
• rs229484
• NM_001346222.1:c.-33-14594G>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.-33-14594G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,124 control chromosomes in the GnomAD database, including 13,568 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 0.41 (13568 hom., cov: 32)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_001346222.1	c.-33-14594G>C		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-14594G>C		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.-33-14594G>C		intron_variant	Intron 1 of 9	4		ENSP00000402685.2
IL2RB	ENST00000445595.2	c.-34+2994G>C		intron_variant	Intron 2 of 10	4		ENSP00000401020.2
IL2RB	ENST00000453962.6	c.-33-14594G>C		intron_variant	Intron 1 of 9	4		ENSP00000403731.2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62849 AN: 152006 Hom.: 13536 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.414 AC: 62928 AN: 152124 Hom.: 13568 Cov.: 32 AF XY: 0.410 AC XY: 30499 AN XY: 74352

African (AFR) AF: 0.546 AC: 22680 AN: 41520

American (AMR) AF: 0.350 AC: 5347 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3464

East Asian (EAS) AF: 0.342 AC: 1769 AN: 5176

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4074 AN: 10568

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25356 AN: 67976

Other (OTH) AF: 0.378 AC: 800 AN: 2116

Alfa AF: 0.222 Hom.: 425

Bravo AF: 0.421

Asia WGS AF: 0.337 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.85
DANN	Benign	0.45
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs229484; hg19: chr22-37554839;