22-37155447-T-C

Position:

• chr22-37155447-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IL2RB	NM_001346222.1	c.-33-11242A>G		intron_variant			NP_001333151.1
IL2RB	NM_001346223.2	c.-33-11242A>G		intron_variant			NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000429622.6	c.-33-11242A>G		intron_variant		4		ENSP00000402685	P4
IL2RB	ENST00000445595.2	c.-34+6346A>G		intron_variant		4		ENSP00000401020	P4
IL2RB	ENST00000453962.6	c.-33-11242A>G		intron_variant		4		ENSP00000403731	P4

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.281

Alfa AF: 0.272 Hom.: 2561

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs743776; hg19: chr22-37551487;