chr22-37133308-C-T

Variant names:

• chr22-37133308-C-T
• rs3218316
• NM_000878.5:c.819-840G>A

Variant summary

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

The NM_000878.5(IL2RB):​c.819-840G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,026 control chromosomes in the GnomAD database, including 1,461 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 0.13 (1461 hom., cov: 32)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RB	NM_000878.5	c.819-840G>A		intron_variant	Intron 8 of 9	ENST00000216223.10	NP_000869.1
IL2RB	NM_001346222.1	c.819-840G>A		intron_variant	Intron 8 of 9		NP_001333151.1
IL2RB	NM_001346223.2	c.819-840G>A		intron_variant	Intron 8 of 9		NP_001333152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RB	ENST00000216223.10	c.819-840G>A		intron_variant	Intron 8 of 9	1	NM_000878.5	ENSP00000216223.5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19552 AN: 151908 Hom.: 1463 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0996

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

GnomAD4 genome AF: 0.129 AC: 19567 AN: 152026 Hom.: 1461 Cov.: 32 AF XY: 0.134 AC XY: 9936 AN XY: 74294

African (AFR) AF: 0.154 AC: 6392 AN: 41480

American (AMR) AF: 0.0687 AC: 1049 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1012 AN: 5160

South Asian (SAS) AF: 0.255 AC: 1228 AN: 4820

European-Finnish (FIN) AF: 0.171 AC: 1806 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7495 AN: 67938

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.124 Hom.: 184

Bravo AF: 0.118

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-1.1
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: rs3218316; hg19: chr22-37529348;