Variant 16-27362859-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.1507T>C(p.Ser503Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,858 control chromosomes in the GnomAD database, including 25,776 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 protective (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4428 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21348 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 0.124

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=0.003134787).

BP6

Variant 16-27362859-T-C is Benign according to our data. Variant chr16-27362859-T-C is described in ClinVar as [protective]. Clinvar id is 14667.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 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.1507T>C	p.Ser503Pro	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.1507T>C	p.Ser503Pro	missense_variant	11/11	1	NM_000418.4	ENSP00000379111	P1	P24394-1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33005

AN:

151926

Hom.:

4411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.159

AC:

39895

AN:

251224

Hom.:

3702

AF XY:

0.152

AC XY:

20640

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0796

Gnomad SAS exome

AF:

0.0968

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.165

AC:

241533

AN:

1461814

Hom.:

21348

Cov.:

AF XY:

0.162

AC XY:

117745

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.0715

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.217

AC:

33065

AN:

152044

Hom.:

4428

Cov.:

AF XY:

0.211

AC XY:

15666

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.380

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.0723

Gnomad4 SAS

AF:

0.0985

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.168

Hom.:

5859

Bravo

AF:

0.227

TwinsUK

AF:

0.170

AC:

630

ALSPAC

AF:

0.173

AC:

668

ESP6500AA

AF:

0.363

AC:

1595

ESP6500EA

AF:

0.162

AC:

1391

ExAC

AF:

0.163

AC:

19843

Asia WGS

AF:

0.131

AC:

456

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.152

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RECLASSIFIED - POLYMORPHISM

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Oct 07, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.44

.;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.24

N;N;.

REVEL

Benign

0.085

Sift

Benign

0.27

T;T;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.54

P;P;.

Vest4

0.14

MPC

0.38

ClinPred

0.012

GERP RS

1.6

Varity_R

0.095

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