rs2243290

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000589.4(IL4):c.361-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,546,350 control chromosomes in the GnomAD database, including 40,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.26 ( 6585 hom., cov: 32)

Exomes 𝑓: 0.18 ( 33516 hom. )

Consequence

IL4
NM_000589.4 intron

Scores

Splicing: ADA: 0.002755

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

68 publications found

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]

IL4 links:

LOC105379176 (HGNC:):

LOC105379176 links:

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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=-0.59).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000589.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL4	NM_000589.4	MANE Select	c.361-9C>A	intron	N/A	NP_000580.1	P05112-1
IL4	NM_172348.3		c.313-9C>A	intron	N/A	NP_758858.1	Q5FC01
IL4	NM_001354990.2		c.*51-9C>A	intron	N/A	NP_001341919.1	U3LVN1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL4	ENST00000231449.7	TSL:1 MANE Select	c.361-9C>A	intron	N/A	ENSP00000231449.2	P05112-1
IL4	ENST00000350025.2	TSL:1	c.313-9C>A	intron	N/A	ENSP00000325190.3	P05112-2
IL4	ENST00000622422.1	TSL:1	c.*51-9C>A	intron	N/A	ENSP00000480581.1	U3LVN1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39083

AN:

151906

Hom.:

6582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.269

AC:

66627

AN:

247594

AF XY:

0.250

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.795

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.181

AC:

252305

AN:

1394326

Hom.:

33516

Cov.:

AF XY:

0.178

AC XY:

124257

AN XY:

697388

show subpopulations

African (AFR)

AF:

0.353

AC:

11307

AN:

32024

American (AMR)

AF:

0.417

AC:

18307

AN:

43874

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

4832

AN:

25644

East Asian (EAS)

AF:

0.739

AC:

29060

AN:

39314

South Asian (SAS)

AF:

0.165

AC:

13850

AN:

83700

European-Finnish (FIN)

AF:

0.344

AC:

18352

AN:

53290

Middle Eastern (MID)

AF:

0.124

AC:

699

AN:

5648

European-Non Finnish (NFE)

AF:

0.137

AC:

143922

AN:

1052742

Other (OTH)

AF:

0.206

AC:

11976

AN:

58090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

8560

17120

25681

34241

42801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5470

10940

16410

21880

27350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.257

AC:

39121

AN:

152024

Hom.:

6585

Cov.:

AF XY:

0.267

AC XY:

19873

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.347

AC:

14395

AN:

41432

American (AMR)

AF:

0.304

AC:

4645

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

662

AN:

3472

East Asian (EAS)

AF:

0.776

AC:

4013

AN:

5174

South Asian (SAS)

AF:

0.191

AC:

919

AN:

4816

European-Finnish (FIN)

AF:

0.360

AC:

3791

AN:

10540

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10152

AN:

67982

Other (OTH)

AF:

0.232

AC:

491

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1319

2638

3958

5277

6596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.187

Hom.:

7481

Bravo

AF:

0.264

Asia WGS

AF:

0.467

AC:

1623

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0028

dbscSNV1_RF

Benign

0.23

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over