chr22-37155447-T-C

Variant names:

• chr22-37155447-T-C
• rs743776
• NM_001346222.1:c.-33-11242A>G

Variant summary

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

The NM_001346222.1(IL2RB):​c.-33-11242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,084 control chromosomes in the GnomAD database, including 6,822 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 0.30 (6822 hom., cov: 32)
• Consequence: IL2RB NM_001346222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_001346222.1	c.-33-11242A>G		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-11242A>G		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.-33-11242A>G		intron_variant	Intron 1 of 9	4		ENSP00000402685.2
IL2RB	ENST00000445595.2	c.-34+6346A>G		intron_variant	Intron 2 of 10	4		ENSP00000401020.2
IL2RB	ENST00000453962.6	c.-33-11242A>G		intron_variant	Intron 1 of 9	4		ENSP00000403731.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45142 AN: 151966 Hom.: 6824 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.297 AC: 45170 AN: 152084 Hom.: 6822 Cov.: 32 AF XY: 0.293 AC XY: 21755 AN XY: 74360

African (AFR) AF: 0.313 AC: 12981 AN: 41466

American (AMR) AF: 0.230 AC: 3521 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3468

East Asian (EAS) AF: 0.120 AC: 622 AN: 5180

South Asian (SAS) AF: 0.165 AC: 795 AN: 4820

European-Finnish (FIN) AF: 0.335 AC: 3537 AN: 10570

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21697 AN: 67970

Other (OTH) AF: 0.281 AC: 593 AN: 2110

Alfa AF: 0.278 Hom.: 3129

Bravo AF: 0.293

Asia WGS AF: 0.164 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		0.066

Splicing

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

Other links and lift over

dbSNP: rs743776; hg19: chr22-37551487;