rs2243269

chr5-132678319-TAA-Tchr5-132678319-TAA-TAchr5-132678319-TAA-TAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000589.4(IL4):c.184-1393_184-1392del 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

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4	NM_000589.4	c.184-1393_184-1392del		intron_variant		ENST00000231449.7
IL4	NM_001354990.2	c.284+440_284+441del		intron_variant
IL4	NM_172348.3	c.136-1393_136-1392del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4	ENST00000231449.7	c.184-1393_184-1392del		intron_variant		1	NM_000589.4	P1
IL4	ENST00000350025.2	c.136-1393_136-1392del		intron_variant		1
IL4	ENST00000622422.1	c.284+440_284+441del		intron_variant		1
IL4	ENST00000495905.1	n.150-1393_150-1392del		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.209

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 v4.3

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: rs2243269; hg19: chr5-132014011;