rs2243252
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2
The NM_000589.4(IL4):c.183+390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00907 in 152,328 control chromosomes in the GnomAD database, including 19 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 0.0091 ( 19 hom., cov: 32)
Consequence
IL4
NM_000589.4 intron
NM_000589.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.42
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00907 (1382/152328) while in subpopulation AFR AF= 0.0288 (1199/41570). AF 95% confidence interval is 0.0275. There are 19 homozygotes in gnomad4. There are 655 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1382 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL4 | NM_000589.4 | c.183+390T>C | intron_variant | ENST00000231449.7 | |||
IL4 | NM_001354990.2 | c.183+390T>C | intron_variant | ||||
IL4 | NM_172348.3 | c.135+711T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL4 | ENST00000231449.7 | c.183+390T>C | intron_variant | 1 | NM_000589.4 | P1 | |||
IL4 | ENST00000350025.2 | c.135+711T>C | intron_variant | 1 | |||||
IL4 | ENST00000622422.1 | c.183+390T>C | intron_variant | 1 | |||||
IL4 | ENST00000495905.1 | n.149+390T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00908 AC: 1382AN: 152210Hom.: 19 Cov.: 32
GnomAD3 genomes
?
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00907 AC: 1382AN: 152328Hom.: 19 Cov.: 32 AF XY: 0.00879 AC XY: 655AN XY: 74490
GnomAD4 genome
?
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1382
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152328
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32
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655
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3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at