Genetic Variant IL2:c.-385T>G (chr4-122456825-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000586.4(IL2):c.-385T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 166,840 control chromosomes in the GnomAD database, including 6,559 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 0.25 ( 5685 hom., cov: 32)

Exomes 𝑓: 0.33 ( 874 hom. )

Consequence

IL2
NM_000586.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

260 publications found

Variant links:

Genes affected

IL2 (HGNC:6001): (interleukin 2) This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli. [provided by RefSeq, Sep 2020]

IL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000586.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	NM_000586.4	MANE Select	c.-385T>G		upstream_gene	N/A	NP_000577.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	ENST00000226730.5	TSL:1 MANE Select	c.-385T>G		upstream_gene	N/A	ENSP00000226730.5

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37699

AN:

151794

Hom.:

5671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.328

AC:

4903

AN:

14926

Hom.:

874

AF XY:

0.331

AC XY:

2429

AN XY:

7336

show subpopulations

African (AFR)

AF:

0.0876

AC:

AN:

548

American (AMR)

AF:

0.318

AC:

347

AN:

1092

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

327

AN:

724

East Asian (EAS)

AF:

0.375

AC:

522

AN:

1392

South Asian (SAS)

AF:

0.515

AC:

236

AN:

458

European-Finnish (FIN)

AF:

0.343

AC:

AN:

274

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.317

AC:

2982

AN:

9416

Other (OTH)

AF:

0.330

AC:

317

AN:

962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

163

327

490

654

817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37733

AN:

151914

Hom.:

5685

Cov.:

AF XY:

0.254

AC XY:

18877

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0737

AC:

3062

AN:

41532

American (AMR)

AF:

0.299

AC:

4552

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1491

AN:

3466

East Asian (EAS)

AF:

0.339

AC:

1747

AN:

5156

South Asian (SAS)

AF:

0.506

AC:

2439

AN:

4824

European-Finnish (FIN)

AF:

0.292

AC:

3084

AN:

10556

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20255

AN:

67832

Other (OTH)

AF:

0.302

AC:

638

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1359

2718

4077

5436

6795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.279

Hom.:

16624

Bravo

AF:

0.237

Asia WGS

AF:

0.422

AC:

1467

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.3

PromoterAI

0.035

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over