4-122451978-T-C

Variant names:

• chr4-122451978-T-C
• rs2069772
• NM_000586.4:c.352-116A>G

Variant summary

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

The NM_000586.4(IL2):​c.352-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 398,536 control chromosomes in the GnomAD database, including 13,724 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 0.20 (4039 hom., cov: 32)
  • Exomes 𝑓: 0.26 (9685 hom.)
• Consequence: IL2 NM_000586.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 54 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	NM_000586.4	MANE Select	c.352-116A>G		intron	N/A	NP_000577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2	ENST00000226730.5	TSL:1 MANE Select	c.352-116A>G		intron	N/A	ENSP00000226730.5	P60568
	IL2	ENST00000477645.1	TSL:3	n.442-116A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30661 AN: 151976 Hom.: 4043 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.264 AC: 65069 AN: 246442 Hom.: 9685 AF XY: 0.265 AC XY: 33473 AN XY: 126376

African (AFR) AF: 0.0605 AC: 403 AN: 6658

American (AMR) AF: 0.142 AC: 1004 AN: 7084

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 1801 AN: 8546

East Asian (EAS) AF: 0.107 AC: 2280 AN: 21392

South Asian (SAS) AF: 0.149 AC: 480 AN: 3230

European-Finnish (FIN) AF: 0.412 AC: 13285 AN: 32238

Middle Eastern (MID) AF: 0.143 AC: 171 AN: 1194

European-Non Finnish (NFE) AF: 0.280 AC: 42281 AN: 150908

Other (OTH) AF: 0.221 AC: 3364 AN: 15192

GnomAD4 genome AF: 0.202 AC: 30649 AN: 152094 Hom.: 4039 Cov.: 32 AF XY: 0.204 AC XY: 15191 AN XY: 74328

African (AFR) AF: 0.0568 AC: 2361 AN: 41560

American (AMR) AF: 0.155 AC: 2361 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5190

South Asian (SAS) AF: 0.139 AC: 669 AN: 4824

European-Finnish (FIN) AF: 0.413 AC: 4353 AN: 10548

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18913 AN: 67924

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.237 Hom.: 9144

Bravo AF: 0.176

Asia WGS AF: 0.111 AC: 388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		0.053
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: rs2069772; hg19: chr4-123373133;