rs56279116

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000589.4(IL4):​c.157G>A​(p.Val53Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,614,096 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00027 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 7 hom. )

Consequence

IL4
NM_000589.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.891
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.003993273).
BS2
High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL4NM_000589.4 linkuse as main transcriptc.157G>A p.Val53Ile missense_variant 2/4 ENST00000231449.7
IL4NM_001354990.2 linkuse as main transcriptc.157G>A p.Val53Ile missense_variant 2/5
IL4NM_172348.3 linkuse as main transcriptc.135+295G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL4ENST00000231449.7 linkuse as main transcriptc.157G>A p.Val53Ile missense_variant 2/41 NM_000589.4 P1P05112-1
IL4ENST00000622422.1 linkuse as main transcriptc.157G>A p.Val53Ile missense_variant 2/51
IL4ENST00000350025.2 linkuse as main transcriptc.135+295G>A intron_variant 1 P05112-2
IL4ENST00000495905.1 linkuse as main transcriptn.123G>A non_coding_transcript_exon_variant 1/25

Frequencies

GnomAD3 genomes
AF:
0.000269
AC:
41
AN:
152196
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00597
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000433
AC:
109
AN:
251474
Hom.:
0
AF XY:
0.000390
AC XY:
53
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00495
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000454
AC:
663
AN:
1461782
Hom.:
7
Cov.:
30
AF XY:
0.000473
AC XY:
344
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0147
Gnomad4 SAS exome
AF:
0.000383
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000269
AC:
41
AN:
152314
Hom.:
1
Cov.:
32
AF XY:
0.000309
AC XY:
23
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00598
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000329
Hom.:
1
Bravo
AF:
0.000227
ExAC
AF:
0.000453
AC:
55
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
6.9
DANN
Benign
0.90
DEOGEN2
Benign
0.33
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.0040
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.69
N;.
REVEL
Benign
0.060
Sift
Benign
0.12
T;.
Sift4G
Benign
0.21
T;T
Polyphen
0.041
B;.
Vest4
0.16
MVP
0.50
MPC
0.25
ClinPred
0.025
T
GERP RS
1.7
Varity_R
0.090
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs56279116; hg19: chr5-132010172; COSMIC: COSV51503102; API