rs1805012

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000418.4(IL4R):c.1291T>C(p.Cys431Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,770 control chromosomes in the GnomAD database, including 9,531 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.098 ( 783 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8748 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.538

Publications

59 publications found

Variant links:

Genes affected

IL4R (HGNC:6015): (interleukin 4 receptor) This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE production. The encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

IL4R Gene-Disease associations (from GenCC):

IgE responsiveness, atopic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

IL4R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018278062).

BP6

Variant 16-27362643-T-C is Benign according to our data. Variant chr16-27362643-T-C is described in ClinVar as Benign. ClinVar VariationId is 3056489.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.1291T>C	p.Cys431Arg	missense_variant	Exon 11 of 11	ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 link	c.1291T>C	p.Cys431Arg	missense_variant	Exon 11 of 11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14904

AN:

152008

Hom.:

783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0856

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0430

Gnomad EAS

AF:

0.0708

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.0950

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0967

GnomAD2 exomes

AF:

0.0961

AC:

24132

AN:

251120

AF XY:

0.0930

show subpopulations

Gnomad AFR exome

AF:

0.0825

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.0448

Gnomad EAS exome

AF:

0.0792

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0895

GnomAD4 exome

AF:

0.107

AC:

156484

AN:

1461644

Hom.:

8748

Cov.:

AF XY:

0.105

AC XY:

76058

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.0859

AC:

2876

AN:

33474

American (AMR)

AF:

0.118

AC:

5273

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

1182

AN:

26136

East Asian (EAS)

AF:

0.0710

AC:

2819

AN:

39698

South Asian (SAS)

AF:

0.0579

AC:

4996

AN:

86248

European-Finnish (FIN)

AF:

0.106

AC:

5670

AN:

53406

Middle Eastern (MID)

AF:

0.0317

AC:

183

AN:

5768

European-Non Finnish (NFE)

AF:

0.115

AC:

127591

AN:

1111802

Other (OTH)

AF:

0.0976

AC:

5894

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

8168

16336

24503

32671

40839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4662

9324

13986

18648

23310

<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:

0.0980

AC:

14910

AN:

152126

Hom.:

783

Cov.:

AF XY:

0.0961

AC XY:

7146

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0855

AC:

3546

AN:

41496

American (AMR)

AF:

0.121

AC:

1846

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0430

AC:

149

AN:

3468

East Asian (EAS)

AF:

0.0708

AC:

366

AN:

5170

South Asian (SAS)

AF:

0.0595

AC:

287

AN:

4820

European-Finnish (FIN)

AF:

0.0950

AC:

1007

AN:

10602

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7485

AN:

67972

Other (OTH)

AF:

0.0961

AC:

203

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

672

1345

2017

2690

3362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.102

Hom.:

1733

Bravo

AF:

0.0968

TwinsUK

AF:

0.118

AC:

439

ALSPAC

AF:

0.119

AC:

458

ESP6500AA

AF:

0.0890

AC:

391

ESP6500EA

AF:

0.108

AC:

925

ExAC

AF:

0.0956

AC:

11606

Asia WGS

AF:

0.0930

AC:

322

AN:

3478

EpiCase

AF:

0.0973

EpiControl

AF:

0.0976

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL4R-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.7

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.19

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.42

.;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.

PhyloP100

-0.54

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.3

D;D;.

REVEL

Benign

0.074

Sift

Benign

0.078

T;T;.

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.97

D;D;.

Vest4

0.11

MPC

0.23

ClinPred

0.048

GERP RS

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over