chr22-37148891-T-G

Variant names:

• chr22-37148891-T-G
• rs228979
• NM_000878.5:c.-34+934A>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.-34+934A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 151,976 control chromosomes in the GnomAD database, including 48,086 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 0.79 (48086 hom., cov: 30)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 12 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 = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5	c.-34+934A>C		intron_variant	Intron 1 of 9	ENST00000216223.10	NP_000869.1
IL2RB	NM_001346222.1	c.-33-4686A>C		intron_variant	Intron 1 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.-33-4686A>C		intron_variant	Intron 1 of 9		NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10	c.-34+934A>C		intron_variant	Intron 1 of 9	1	NM_000878.5	ENSP00000216223.5

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120048 AN: 151858 Hom.: 48027 Cov.: 30

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.791 AC: 120165 AN: 151976 Hom.: 48086 Cov.: 30 AF XY: 0.790 AC XY: 58682 AN XY: 74304

African (AFR) AF: 0.929 AC: 38497 AN: 41458

American (AMR) AF: 0.761 AC: 11615 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2743 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3716 AN: 5154

South Asian (SAS) AF: 0.751 AC: 3616 AN: 4814

European-Finnish (FIN) AF: 0.764 AC: 8079 AN: 10576

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49199 AN: 67924

Other (OTH) AF: 0.770 AC: 1625 AN: 2110

Alfa AF: 0.749 Hom.: 135402

Bravo AF: 0.797

Asia WGS AF: 0.740 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.38
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs228979; hg19: chr22-37544931;