rs2070874
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000589.4(IL4):c.-33C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,602,216 control chromosomes in the GnomAD database, including 42,660 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 0.28 ( 7669 hom., cov: 32)
Exomes 𝑓: 0.18 ( 34991 hom. )
Consequence
IL4
NM_000589.4 5_prime_UTR
NM_000589.4 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.152
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL4 | NM_000589.4 | c.-33C>T | 5_prime_UTR_variant | 1/4 | ENST00000231449.7 | ||
IL4 | NM_001354990.2 | c.-33C>T | 5_prime_UTR_variant | 1/5 | |||
IL4 | NM_172348.3 | c.-33C>T | 5_prime_UTR_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL4 | ENST00000231449.7 | c.-33C>T | 5_prime_UTR_variant | 1/4 | 1 | NM_000589.4 | P1 | ||
IL4 | ENST00000622422.1 | c.-33C>T | 5_prime_UTR_variant | 1/5 | 1 | ||||
IL4 | ENST00000350025.2 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.277 AC: 42143AN: 151898Hom.: 7661 Cov.: 32
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GnomAD3 exomes AF: 0.276 AC: 69369AN: 250924Hom.: 14266 AF XY: 0.255 AC XY: 34617AN XY: 135604
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GnomAD4 exome AF: 0.180 AC: 260836AN: 1450200Hom.: 34991 Cov.: 30 AF XY: 0.177 AC XY: 127785AN XY: 721696
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GnomAD4 genome AF: 0.278 AC: 42189AN: 152016Hom.: 7669 Cov.: 32 AF XY: 0.287 AC XY: 21329AN XY: 74292
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ClinVar
Not reported inComputational scores
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Name
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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