22-37128240-G-T

Variant names:

• chr22-37128240-G-T
• rs1379563593
• NM_000878.5:c.1512C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000878.5(IL2RB):​c.1512C>A​(p.Gly504Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G504G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: IL2RB NM_000878.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 0 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, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000878.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	NM_000878.5	MANE Select	c.1512C>A	p.Gly504Gly	synonymous	Exon 10 of 10	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.1512C>A	p.Gly504Gly	synonymous	Exon 10 of 10	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.1512C>A	p.Gly504Gly	synonymous	Exon 10 of 10	NP_001333152.1	P14784

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB	ENST00000216223.10	TSL:1 MANE Select	c.1512C>A	p.Gly504Gly	synonymous	Exon 10 of 10	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.1530C>A	p.Gly510Gly	synonymous	Exon 10 of 10	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.1512C>A	p.Gly504Gly	synonymous	Exon 10 of 10	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351670 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 661212

African (AFR) AF: 0.00 AC: 0 AN: 29622

American (AMR) AF: 0.00 AC: 0 AN: 26930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19602

East Asian (EAS) AF: 0.00 AC: 0 AN: 37194

South Asian (SAS) AF: 0.00 AC: 0 AN: 68340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5264

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059772

Other (OTH) AF: 0.00 AC: 0 AN: 55400

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.32
PhyloP100		-0.28

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: rs1379563593; hg19: chr22-37524280;