Variant rs1801275 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000418.4(IL4R):c.1727A>G(p.Gln576Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,613,910 control chromosomes in the GnomAD database, including 54,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 12743 hom., cov: 33)

Exomes 𝑓: 0.22 ( 41529 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.05

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1686489E-6).

BP6

Variant 16-27363079-A-G is Benign according to our data. Variant chr16-27363079-A-G is described in ClinVar as [Benign]. Clinvar id is 14665.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4 linkuse as main transcript	c.1727A>G	p.Gln576Arg	missense_variant	11/11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 linkuse as main transcript	c.1727A>G	p.Gln576Arg	missense_variant	11/11	1	NM_000418.4	ENSP00000379111	P1	P24394-1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52747

AN:

152070

Hom.:

12686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.688

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.248

AC:

61954

AN:

250126

Hom.:

9564

AF XY:

0.235

AC XY:

31920

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.703

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.225

AC:

328389

AN:

1461722

Hom.:

41529

Cov.:

AF XY:

0.222

AC XY:

161640

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.707

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.347

AC:

52863

AN:

152188

Hom.:

12743

Cov.:

AF XY:

0.343

AC XY:

25484

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.688

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.226

Hom.:

10956

Bravo

AF:

0.369

TwinsUK

AF:

0.211

AC:

781

ALSPAC

AF:

0.215

AC:

829

ESP6500AA

AF:

0.674

AC:

2963

ESP6500EA

AF:

0.204

AC:

1753

ExAC

AF:

0.254

AC:

30865

Asia WGS

AF:

0.278

AC:

967

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RECLASSIFIED - POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Feb 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.074

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.22

.;T;T

MetaRNN

Benign

0.0000012

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

N;N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

0.89

N;N;.

REVEL

Benign

0.065

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.031

MPC

0.14

ClinPred

0.00026

GERP RS

2.8

Varity_R

0.018

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over