chr22-37127681-C-G

Position:

• chr22-37127681-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000878.5(IL2RB):​c.*415G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 157,788 control chromosomes in the GnomAD database, including 10,966 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 0.36 (10674 hom., cov: 31)
  • Exomes 𝑓: 0.29 (292 hom.)
• Consequence: IL2RB NM_000878.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RB	NM_000878.5	c.*415G>C		3_prime_UTR_variant	10/10	ENST00000216223.10
IL2RB	NM_001346222.1	c.*415G>C		3_prime_UTR_variant	10/10
IL2RB	NM_001346223.2	c.*415G>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RB	ENST00000216223.10	c.*415G>C		3_prime_UTR_variant	10/10	1	NM_000878.5	P4

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54661 AN: 151312 Hom.: 10646 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.288 AC: 1831 AN: 6358 Hom.: 292 Cov.: 0 AF XY: 0.289 AC XY: 942 AN XY: 3262

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.361 AC: 54735 AN: 151430 Hom.: 10674 Cov.: 31 AF XY: 0.362 AC XY: 26765 AN XY: 73962

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.328

Alfa AF: 0.278 Hom.: 3402

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs228941; hg19: chr22-37523721;