22-37143673-T-C

Variant names:

• chr22-37143673-T-C
• rs2235330
• NM_000878.5:c.89-38A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000878.5(IL2RB):​c.89-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,431,338 control chromosomes in the GnomAD database, including 31,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3144 hom., cov: 31)
  • Exomes 𝑓: 0.20 (27901 hom.)
• Consequence: IL2RB NM_000878.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39
• Publications: 21 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-37143673-T-C is Benign according to our data. Variant chr22-37143673-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

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.89-38A>G		intron	N/A	NP_000869.1	P14784
	IL2RB	NM_001346222.1		c.89-38A>G		intron	N/A	NP_001333151.1	P14784
	IL2RB	NM_001346223.2		c.89-38A>G		intron	N/A	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.89-38A>G		intron	N/A	ENSP00000216223.5	P14784
	IL2RB	ENST00000698894.2		c.89-38A>G		intron	N/A	ENSP00000514013.1	A0A8V8TMD3
	IL2RB	ENST00000429622.6	TSL:4	c.89-38A>G		intron	N/A	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27867 AN: 151632 Hom.: 3141 Cov.: 31

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.221 AC: 55065 AN: 249204 AF XY: 0.211

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.439

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.199 AC: 254896 AN: 1279588 Hom.: 27901 Cov.: 19 AF XY: 0.195 AC XY: 126185 AN XY: 645822

African (AFR) AF: 0.0840 AC: 2504 AN: 29792

American (AMR) AF: 0.332 AC: 14703 AN: 44322

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4350 AN: 24952

East Asian (EAS) AF: 0.408 AC: 15813 AN: 38724

South Asian (SAS) AF: 0.121 AC: 9976 AN: 82446

European-Finnish (FIN) AF: 0.258 AC: 13641 AN: 52782

Middle Eastern (MID) AF: 0.0992 AC: 539 AN: 5434

European-Non Finnish (NFE) AF: 0.193 AC: 182934 AN: 946798

Other (OTH) AF: 0.192 AC: 10436 AN: 54338

GnomAD4 genome AF: 0.184 AC: 27872 AN: 151750 Hom.: 3144 Cov.: 31 AF XY: 0.189 AC XY: 14025 AN XY: 74130

African (AFR) AF: 0.0885 AC: 3661 AN: 41374

American (AMR) AF: 0.255 AC: 3886 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3466

East Asian (EAS) AF: 0.434 AC: 2225 AN: 5124

South Asian (SAS) AF: 0.122 AC: 587 AN: 4798

European-Finnish (FIN) AF: 0.268 AC: 2833 AN: 10554

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13414 AN: 67872

Other (OTH) AF: 0.175 AC: 368 AN: 2098

Alfa AF: 0.190 Hom.: 6524

Bravo AF: 0.183

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.089
DANN	Benign	0.61
PhyloP100		-1.4
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: rs2235330; hg19: chr22-37539713;