rs2243268

Variant names:

• chr5-132678271-A-C
• rs2243268
• NM_000589.4:c.184-1443A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132678271-A-C
• chr5-132678271-A-G
• chr5-132678271-A-T

Variant summary

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

The NM_000589.4(IL4):​c.184-1443A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,122 control chromosomes in the GnomAD database, including 5,444 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 0.23 (5444 hom., cov: 33)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 63 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4	NM_000589.4	c.184-1443A>C		intron_variant	Intron 2 of 3	ENST00000231449.7	NP_000580.1
IL4	NM_172348.3	c.136-1443A>C		intron_variant	Intron 1 of 2		NP_758858.1
IL4	NM_001354990.2	c.284+390A>C		intron_variant	Intron 3 of 4		NP_001341919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.184-1443A>C		intron_variant	Intron 2 of 3	1	NM_000589.4	ENSP00000231449.2
IL4	ENST00000350025.2	c.136-1443A>C		intron_variant	Intron 1 of 2	1		ENSP00000325190.3
IL4	ENST00000622422.1	c.284+390A>C		intron_variant	Intron 3 of 4	1		ENSP00000480581.1
IL4	ENST00000495905.1	n.150-1443A>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35362 AN: 152004 Hom.: 5447 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.233 AC: 35388 AN: 152122 Hom.: 5444 Cov.: 33 AF XY: 0.244 AC XY: 18179 AN XY: 74384

African (AFR) AF: 0.263 AC: 10900 AN: 41470

American (AMR) AF: 0.295 AC: 4513 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3999 AN: 5174

South Asian (SAS) AF: 0.192 AC: 928 AN: 4826

European-Finnish (FIN) AF: 0.359 AC: 3787 AN: 10556

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

European-Non Finnish (NFE) AF: 0.149 AC: 10113 AN: 68006

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.173 Hom.: 3500

Bravo AF: 0.236

Asia WGS AF: 0.453 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		0.30
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: rs2243268; hg19: chr5-132013963;