4-122452742-G-A

Variant names:

• chr4-122452742-G-A
• rs2069779
• NM_000586.4:c.352-880C>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.352-880C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 151,892 control chromosomes in the GnomAD database, including 259 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 0.049 (259 hom., cov: 32)
• Consequence: IL2 NM_000586.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 15 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2	NM_000586.4	c.352-880C>T		intron_variant	Intron 3 of 3	ENST00000226730.5	NP_000577.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2	ENST00000226730.5	c.352-880C>T		intron_variant	Intron 3 of 3	1	NM_000586.4	ENSP00000226730.5
IL2	ENST00000477645.1	n.442-880C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7481 AN: 151774 Hom.: 259 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0396

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0492 AC: 7473 AN: 151892 Hom.: 259 Cov.: 32 AF XY: 0.0499 AC XY: 3701 AN XY: 74222

African (AFR) AF: 0.0104 AC: 430 AN: 41508

American (AMR) AF: 0.0381 AC: 580 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0396 AC: 137 AN: 3462

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4820

European-Finnish (FIN) AF: 0.0944 AC: 997 AN: 10562

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5030 AN: 67826

Other (OTH) AF: 0.0443 AC: 93 AN: 2098

Alfa AF: 0.0613 Hom.: 57

Bravo AF: 0.0427

Asia WGS AF: 0.0130 AC: 46 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.2
DANN	Benign	0.32
PhyloP100		1.0
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: rs2069779; hg19: chr4-123373897;