Variant 16-27362643-T-C 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.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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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=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 id 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/exons	MANE	Protein	UniProt
IL4R	NM_000418.4 linkuse as main transcript	c.1291T>C	p.Cys431Arg	missense_variant	11/11	ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 linkuse as main transcript	c.1291T>C	p.Cys431Arg	missense_variant	11/11	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

GnomAD3 exomes

AF:

0.0961

AC:

24132

AN:

251120

Hom.:

1217

AF XY:

0.0930

AC XY:

12625

AN XY:

135738

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 SAS exome

AF:

0.0554

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

Gnomad4 AFR exome

AF:

0.0859

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.0710

Gnomad4 SAS exome

AF:

0.0579

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.0976

GnomAD4 genome

AF:

0.0980

AC:

14910

AN:

152126

Hom.:

783

Cov.:

AF XY:

0.0961

AC XY:

7146

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0855

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.0430

Gnomad4 EAS

AF:

0.0708

Gnomad4 SAS

AF:

0.0595

Gnomad4 FIN

AF:

0.0950

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0961

Alfa

AF:

0.101

Hom.:

1245

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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

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;.

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

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