5-132678417-A-G

Variant names:

• chr5-132678417-A-G
• rs2243270
• NM_000589.4:c.184-1297A>G

Variant summary

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

The NM_000589.4(IL4):​c.184-1297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,160 control chromosomes in the GnomAD database, including 13,003 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 0.35 (13003 hom., cov: 33)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 47 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	NM_000589.4	MANE Select	c.184-1297A>G		intron	N/A	NP_000580.1	P05112-1
	IL4	NM_172348.3		c.136-1297A>G		intron	N/A	NP_758858.1	Q5FC01
	IL4	NM_001354990.2		c.284+536A>G		intron	N/A	NP_001341919.1	U3LVN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	ENST00000231449.7	TSL:1 MANE Select	c.184-1297A>G		intron	N/A	ENSP00000231449.2	P05112-1
	IL4	ENST00000350025.2	TSL:1	c.136-1297A>G		intron	N/A	ENSP00000325190.3	P05112-2
	IL4	ENST00000622422.1	TSL:1	c.284+536A>G		intron	N/A	ENSP00000480581.1	U3LVN1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52749 AN: 152042 Hom.: 12974 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.347 AC: 52834 AN: 152160 Hom.: 13003 Cov.: 33 AF XY: 0.354 AC XY: 26321 AN XY: 74390

African (AFR) AF: 0.641 AC: 26597 AN: 41490

American (AMR) AF: 0.347 AC: 5304 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.773 AC: 4001 AN: 5178

South Asian (SAS) AF: 0.194 AC: 937 AN: 4826

European-Finnish (FIN) AF: 0.363 AC: 3833 AN: 10568

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10729 AN: 68022

Other (OTH) AF: 0.300 AC: 635 AN: 2114

Alfa AF: 0.226 Hom.: 16313

Bravo AF: 0.367

Asia WGS AF: 0.484 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.52
PhyloP100		-0.73
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: rs2243270; hg19: chr5-132014109;