chr5-132677607-C-G

Variant names:

• chr5-132677607-C-G
• rs2243263
• NM_000589.4:c.184-2107C>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.184-2107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,286 control chromosomes in the GnomAD database, including 58,195 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 0.87 (58195 hom., cov: 33)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4	NM_000589.4	c.184-2107C>G		intron_variant	Intron 2 of 3	ENST00000231449.7	NP_000580.1
IL4	NM_172348.3	c.136-2107C>G		intron_variant	Intron 1 of 2		NP_758858.1
IL4	NM_001354990.2	c.184-174C>G		intron_variant	Intron 2 of 4		NP_001341919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.184-2107C>G		intron_variant	Intron 2 of 3	1	NM_000589.4	ENSP00000231449.2
IL4	ENST00000350025.2	c.136-2107C>G		intron_variant	Intron 1 of 2	1		ENSP00000325190.3
IL4	ENST00000622422.1	c.184-174C>G		intron_variant	Intron 2 of 4	1		ENSP00000480581.1
IL4	ENST00000495905.1	n.150-2107C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132911 AN: 152168 Hom.: 58162 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.873 AC: 133001 AN: 152286 Hom.: 58195 Cov.: 33 AF XY: 0.872 AC XY: 64948 AN XY: 74460

African (AFR) AF: 0.833 AC: 34606 AN: 41552

American (AMR) AF: 0.868 AC: 13278 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3013 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4841 AN: 5188

South Asian (SAS) AF: 0.837 AC: 4045 AN: 4830

European-Finnish (FIN) AF: 0.902 AC: 9562 AN: 10600

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60743 AN: 68028

Other (OTH) AF: 0.869 AC: 1835 AN: 2112

Alfa AF: 0.872 Hom.: 2874

Bravo AF: 0.868

Asia WGS AF: 0.900 AC: 3132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.73
PhyloP100		0.074
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: rs2243263; hg19: chr5-132013299;