chr5-132679140-G-A

Variant names:

• chr5-132679140-G-A
• rs2243274
• NM_000589.4:c.184-574G>A

Variant summary

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

The NM_000589.4(IL4):​c.184-574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,072 control chromosomes in the GnomAD database, including 12,080 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 (12080 hom., cov: 32)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 37 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=-0.9).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	NM_000589.4	MANE Select	c.184-574G>A		intron	N/A	NP_000580.1
	LOC105379176	NR_134248.1		n.1153C>T		non_coding_transcript_exon	Exon 2 of 2
	IL4	NM_172348.3		c.136-574G>A		intron	N/A	NP_758858.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	ENST00000231449.7	TSL:1 MANE Select	c.184-574G>A		intron	N/A	ENSP00000231449.2
	IL4	ENST00000350025.2	TSL:1	c.136-574G>A		intron	N/A	ENSP00000325190.3
	IL4	ENST00000622422.1	TSL:1	c.285-574G>A		intron	N/A	ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51164 AN: 151954 Hom.: 12051 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.337 AC: 51250 AN: 152072 Hom.: 12080 Cov.: 32 AF XY: 0.344 AC XY: 25563 AN XY: 74334

African (AFR) AF: 0.608 AC: 25218 AN: 41460

American (AMR) AF: 0.339 AC: 5187 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3982 AN: 5152

South Asian (SAS) AF: 0.193 AC: 932 AN: 4820

European-Finnish (FIN) AF: 0.363 AC: 3847 AN: 10586

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10679 AN: 67962

Other (OTH) AF: 0.294 AC: 620 AN: 2112

Alfa AF: 0.191 Hom.: 1510

Bravo AF: 0.355

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.44
PhyloP100		0.14
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: rs2243274; hg19: chr5-132014832;