rs2070874

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152
Variant links:
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
IL4NM_000589.4 linkuse as main transcriptc.-33C>T 5_prime_UTR_variant 1/4 ENST00000231449.7
IL4NM_001354990.2 linkuse as main transcriptc.-33C>T 5_prime_UTR_variant 1/5
IL4NM_172348.3 linkuse as main transcriptc.-33C>T 5_prime_UTR_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL4ENST00000231449.7 linkuse as main transcriptc.-33C>T 5_prime_UTR_variant 1/41 NM_000589.4 P1P05112-1
IL4ENST00000622422.1 linkuse as main transcriptc.-33C>T 5_prime_UTR_variant 1/51
IL4ENST00000350025.2 linkuse as main transcript upstream_gene_variant 1 P05112-2

Frequencies

GnomAD3 genomes
AF:
0.277
AC:
42143
AN:
151898
Hom.:
7661
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.416
Gnomad AMI
AF:
0.0164
Gnomad AMR
AF:
0.310
Gnomad ASJ
AF:
0.229
Gnomad EAS
AF:
0.776
Gnomad SAS
AF:
0.192
Gnomad FIN
AF:
0.359
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.149
Gnomad OTH
AF:
0.240
GnomAD3 exomes
AF:
0.276
AC:
69369
AN:
250924
Hom.:
14266
AF XY:
0.255
AC XY:
34617
AN XY:
135604
show subpopulations
Gnomad AFR exome
AF:
0.423
Gnomad AMR exome
AF:
0.442
Gnomad ASJ exome
AF:
0.230
Gnomad EAS exome
AF:
0.792
Gnomad SAS exome
AF:
0.166
Gnomad FIN exome
AF:
0.351
Gnomad NFE exome
AF:
0.145
Gnomad OTH exome
AF:
0.217
GnomAD4 exome
AF:
0.180
AC:
260836
AN:
1450200
Hom.:
34991
Cov.:
30
AF XY:
0.177
AC XY:
127785
AN XY:
721696
show subpopulations
Gnomad4 AFR exome
AF:
0.416
Gnomad4 AMR exome
AF:
0.426
Gnomad4 ASJ exome
AF:
0.227
Gnomad4 EAS exome
AF:
0.736
Gnomad4 SAS exome
AF:
0.164
Gnomad4 FIN exome
AF:
0.343
Gnomad4 NFE exome
AF:
0.134
Gnomad4 OTH exome
AF:
0.210
GnomAD4 genome
AF:
0.278
AC:
42189
AN:
152016
Hom.:
7669
Cov.:
32
AF XY:
0.287
AC XY:
21329
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.416
Gnomad4 AMR
AF:
0.310
Gnomad4 ASJ
AF:
0.229
Gnomad4 EAS
AF:
0.775
Gnomad4 SAS
AF:
0.192
Gnomad4 FIN
AF:
0.359
Gnomad4 NFE
AF:
0.149
Gnomad4 OTH
AF:
0.242
Alfa
AF:
0.168
Hom.:
3121
Bravo
AF:
0.287
Asia WGS
AF:
0.462
AC:
1606
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
4.8
DANN
Benign
0.82

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2070874; hg19: chr5-132009710; API