rs2243269

Variant names:

• chr5-132678319-TAA-T
• rs2243269
• NM_000589.4:c.184-1393_184-1392delAA

Your query was ambiguous. Multiple possible variants found:

• chr5-132678319-TAA-T
• chr5-132678319-TAA-TA
• chr5-132678319-TAA-TAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000589.4(IL4):​c.184-1393_184-1392delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,076 control chromosomes in the GnomAD database, including 5,506 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5506 hom., cov: 27)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 1 publications found

Genes affected

IL4 (HGNC:6014): (interleukin 4) The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. IL4 is considered an important cytokine for tissue repair, counterbalancing the effects of proinflammatory type 1 cytokines, however, it also promotes allergic airway inflammation. Moreover, IL-4, a type 2 cytokine, mediates and regulates a variety of human host responses such as allergic, anti-parasitic, wound healing, and acute inflammation. This cytokine has been reported to promote resolution of neutrophil-mediated acute lung injury. In an allergic response, IL-4 has an essential role in the production of allergen-specific immunoglobin (Ig) E. This pro-inflammatory cytokine has been observed to be increased in COVID-19 (Coronavirus disease 2019) patients, but is not necessarily associated with severe COVID-19 pathology. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000589.4. 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
	IL4	NM_000589.4	MANE Select	c.184-1393_184-1392delAA		intron	N/A	NP_000580.1
	IL4	NM_172348.3		c.136-1393_136-1392delAA		intron	N/A	NP_758858.1
	IL4	NM_001354990.2		c.284+440_284+441delAA		intron	N/A	NP_001341919.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	ENST00000231449.7	TSL:1 MANE Select	c.184-1394_184-1393delAA		intron	N/A	ENSP00000231449.2
	IL4	ENST00000350025.2	TSL:1	c.136-1394_136-1393delAA		intron	N/A	ENSP00000325190.3
	IL4	ENST00000622422.1	TSL:1	c.284+439_284+440delAA		intron	N/A	ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35672 AN: 151958 Hom.: 5510 Cov.: 27

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.235 AC: 35700 AN: 152076 Hom.: 5506 Cov.: 27 AF XY: 0.246 AC XY: 18319 AN XY: 74340

African (AFR) AF: 0.271 AC: 11246 AN: 41474

American (AMR) AF: 0.295 AC: 4521 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3468

East Asian (EAS) AF: 0.772 AC: 3989 AN: 5164

South Asian (SAS) AF: 0.192 AC: 923 AN: 4818

European-Finnish (FIN) AF: 0.358 AC: 3769 AN: 10536

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10102 AN: 67996

Other (OTH) AF: 0.209 AC: 442 AN: 2112

Alfa AF: 0.204 Hom.: 445

Bravo AF: 0.239

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.074
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: rs2243269; hg19: chr5-132014011;