chr4-122456327-C-A

Variant names:

• chr4-122456327-C-A
• rs2069763
• NM_000586.4:c.114G>T

Variant summary

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

The NM_000586.4(IL2):​c.114G>T​(p.Leu38Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,606,330 control chromosomes in the GnomAD database, including 93,631 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 0.29 (7518 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86113 hom.)
• Consequence: IL2 NM_000586.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 200 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 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.114G>T	p.Leu38Leu	synonymous	Exon 1 of 4	NP_000577.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	ENST00000226730.5	TSL:1 MANE Select	c.114G>T	p.Leu38Leu	synonymous	Exon 1 of 4	ENSP00000226730.5
	IL2	ENST00000477645.1	TSL:3	n.114G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43941 AN: 151608 Hom.: 7517 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.271

GnomAD2 exomes AF: 0.356 AC: 88751 AN: 249066 AF XY: 0.347

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.335 AC: 487565 AN: 1454604 Hom.: 86113 Cov.: 32 AF XY: 0.332 AC XY: 240311 AN XY: 723892

African (AFR) AF: 0.0987 AC: 3296 AN: 33390

American (AMR) AF: 0.487 AC: 21627 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5729 AN: 26014

East Asian (EAS) AF: 0.492 AC: 19476 AN: 39594

South Asian (SAS) AF: 0.270 AC: 23245 AN: 86056

European-Finnish (FIN) AF: 0.470 AC: 25059 AN: 53302

Middle Eastern (MID) AF: 0.166 AC: 951 AN: 5746

European-Non Finnish (NFE) AF: 0.335 AC: 370198 AN: 1105938

Other (OTH) AF: 0.299 AC: 17984 AN: 60116

GnomAD4 genome AF: 0.290 AC: 43943 AN: 151726 Hom.: 7518 Cov.: 32 AF XY: 0.297 AC XY: 21980 AN XY: 74130

African (AFR) AF: 0.116 AC: 4796 AN: 41440

American (AMR) AF: 0.395 AC: 6004 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3462

East Asian (EAS) AF: 0.477 AC: 2458 AN: 5156

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4828

European-Finnish (FIN) AF: 0.472 AC: 4972 AN: 10536

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22917 AN: 67800

Other (OTH) AF: 0.271 AC: 571 AN: 2104

Alfa AF: 0.318 Hom.: 22765

Bravo AF: 0.279

Asia WGS AF: 0.300 AC: 1042 AN: 3478

EpiCase AF: 0.309

EpiControl AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		-0.076
PromoterAI		-0.0016	Neutral
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: rs2069763; hg19: chr4-123377482; COSMIC: COSV56985306;