chr22-37141018-C-G

Variant names:

• chr22-37141018-C-G
• rs228965
• NM_000878.5:c.282+1416G>C

Variant summary

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

The NM_000878.5(IL2RB):​c.282+1416G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,018 control chromosomes in the GnomAD database, including 24,589 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 0.54 (24589 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.10
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5	c.282+1416G>C		intron_variant	Intron 4 of 9	ENST00000216223.10	NP_000869.1
IL2RB	NM_001346222.1	c.282+1416G>C		intron_variant	Intron 4 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.282+1416G>C		intron_variant	Intron 4 of 9		NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10	c.282+1416G>C		intron_variant	Intron 4 of 9	1	NM_000878.5	ENSP00000216223.5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82274 AN: 151898 Hom.: 24541 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.542 AC: 82365 AN: 152018 Hom.: 24589 Cov.: 32 AF XY: 0.543 AC XY: 40353 AN XY: 74318

African (AFR) AF: 0.809 AC: 33559 AN: 41480

American (AMR) AF: 0.451 AC: 6894 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3470

East Asian (EAS) AF: 0.622 AC: 3207 AN: 5156

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4814

European-Finnish (FIN) AF: 0.479 AC: 5066 AN: 10570

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28836 AN: 67932

Other (OTH) AF: 0.466 AC: 985 AN: 2112

Alfa AF: 0.329 Hom.: 911

Bravo AF: 0.553

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.030
DANN	Benign	0.050
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs228965; hg19: chr22-37537058;