5-132682252-A-G

Variant names:

• chr5-132682252-A-G
• rs2243288
• NM_000589.4:c.361-234A>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.361-234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 150,096 control chromosomes in the GnomAD database, including 11,860 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 0.34 (11860 hom., cov: 31)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 25 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]

LOC105379176 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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.361-234A>G		intron	N/A	NP_000580.1
	IL4	NM_172348.3		c.313-234A>G		intron	N/A	NP_758858.1
	IL4	NM_001354990.2		c.*51-234A>G		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.361-234A>G		intron	N/A	ENSP00000231449.2
	IL4	ENST00000350025.2	TSL:1	c.313-234A>G		intron	N/A	ENSP00000325190.3
	IL4	ENST00000622422.1	TSL:1	c.*51-234A>G		intron	N/A	ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 50712 AN: 149978 Hom.: 11829 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.0170

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.338 AC: 50802 AN: 150096 Hom.: 11860 Cov.: 31 AF XY: 0.346 AC XY: 25321 AN XY: 73234

African (AFR) AF: 0.603 AC: 24823 AN: 41160

American (AMR) AF: 0.341 AC: 5158 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 716 AN: 3450

East Asian (EAS) AF: 0.777 AC: 3991 AN: 5134

South Asian (SAS) AF: 0.204 AC: 934 AN: 4582

European-Finnish (FIN) AF: 0.373 AC: 3801 AN: 10184

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.159 AC: 10689 AN: 67202

Other (OTH) AF: 0.299 AC: 621 AN: 2080

Alfa AF: 0.182 Hom.: 1915

Bravo AF: 0.353

Asia WGS AF: 0.484 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.25
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2243288; hg19: chr5-132017944; COSMIC: COSV51503574; COSMIC: COSV51503574;