chr5-132676418-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000589.4(IL4):​c.183+1912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 152,244 control chromosomes in the GnomAD database, including 50 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 0.016 ( 50 hom., cov: 31)

Consequence

IL4
NM_000589.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.173
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.016 (2435/152244) while in subpopulation AFR AF = 0.0491 (2038/41532). AF 95% confidence interval is 0.0473. There are 50 homozygotes in GnomAd4. There are 1132 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
BS2
High AC in GnomAd4 at 2435 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL4NM_000589.4 linkc.183+1912C>T intron_variant Intron 2 of 3 ENST00000231449.7 NP_000580.1 P05112-1D4HNR6
IL4NM_172348.3 linkc.135+2233C>T intron_variant Intron 1 of 2 NP_758858.1 P05112-2Q5FC01
IL4NM_001354990.2 linkc.184-1363C>T intron_variant Intron 2 of 4 NP_001341919.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL4ENST00000231449.7 linkc.183+1912C>T intron_variant Intron 2 of 3 1 NM_000589.4 ENSP00000231449.2 P05112-1
IL4ENST00000350025.2 linkc.135+2233C>T intron_variant Intron 1 of 2 1 ENSP00000325190.3 P05112-2
IL4ENST00000622422.1 linkc.184-1363C>T intron_variant Intron 2 of 4 1 ENSP00000480581.1 U3LVN1
IL4ENST00000495905.1 linkn.149+1912C>T intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
AF:
0.0159
AC:
2426
AN:
152126
Hom.:
50
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0490
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0115
Gnomad ASJ
AF:
0.0156
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.00166
Gnomad OTH
AF:
0.0172
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0160
AC:
2435
AN:
152244
Hom.:
50
Cov.:
31
AF XY:
0.0152
AC XY:
1132
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0491
AC:
0.0490706
AN:
0.0490706
Gnomad4 AMR
AF:
0.0115
AC:
0.0115078
AN:
0.0115078
Gnomad4 ASJ
AF:
0.0156
AC:
0.0155709
AN:
0.0155709
Gnomad4 EAS
AF:
0.000579
AC:
0.000578704
AN:
0.000578704
Gnomad4 SAS
AF:
0.00124
AC:
0.00124327
AN:
0.00124327
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.00166
AC:
0.00166162
AN:
0.00166162
Gnomad4 OTH
AF:
0.0170
AC:
0.0170455
AN:
0.0170455
Heterozygous variant carriers
0
117
235
352
470
587
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
24
48
72
96
120
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0149
Hom.:
6
Bravo
AF:
0.0193
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.5
DANN
Benign
0.66
Mutation Taster
=100/0
polymorphism

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: rs2243258; hg19: chr5-132012110; API