4-122451978-T-C

Position:

• chr4-122451978-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2	NM_000586.4	c.352-116A>G		intron_variant		ENST00000226730.5	NP_000577.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2	ENST00000226730.5	c.352-116A>G		intron_variant		1	NM_000586.4	ENSP00000226730.5
IL2	ENST00000477645.1	n.442-116A>G		intron_variant		3

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

Gnomad4 AFR exome AF: 0.0605

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.221

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

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.192

Alfa AF: 0.246 Hom.: 5696

Bravo AF: 0.176

Asia WGS AF: 0.111 AC: 388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2069772; hg19: chr4-123373133;