rs2243284

Variant names:

• chr5-132681300-G-A
• rs2243284
• NM_000589.4:c.361-1186G>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.361-1186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,872 control chromosomes in the GnomAD database, including 11,587 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 0.33 (11587 hom., cov: 31)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4	NM_000589.4	c.361-1186G>A		intron_variant	Intron 3 of 3	ENST00000231449.7	NP_000580.1
IL4	NM_172348.3	c.313-1186G>A		intron_variant	Intron 2 of 2		NP_758858.1
IL4	NM_001354990.2	c.*51-1186G>A		intron_variant	Intron 4 of 4		NP_001341919.1
LOC105379176	NR_134248.1	n.176+1154C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.361-1186G>A		intron_variant	Intron 3 of 3	1	NM_000589.4	ENSP00000231449.2
IL4	ENST00000350025.2	c.313-1186G>A		intron_variant	Intron 2 of 2	1		ENSP00000325190.3
IL4	ENST00000622422.1	c.*51-1186G>A		intron_variant	Intron 4 of 4	1		ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50280 AN: 151754 Hom.: 11561 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.332 AC: 50364 AN: 151872 Hom.: 11587 Cov.: 31 AF XY: 0.339 AC XY: 25168 AN XY: 74244

African (AFR) AF: 0.590 AC: 24365 AN: 41326

American (AMR) AF: 0.337 AC: 5144 AN: 15262

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

East Asian (EAS) AF: 0.776 AC: 4007 AN: 5166

South Asian (SAS) AF: 0.194 AC: 933 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3836 AN: 10550

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10676 AN: 67968

Other (OTH) AF: 0.293 AC: 617 AN: 2106

Alfa AF: 0.266 Hom.: 913

Bravo AF: 0.349

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		-0.086
Mutation Taster		=99/1	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: rs2243284; hg19: chr5-132016992;