16-27342158-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000418.4(IL4R):c.108C>T(p.Ser36Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,190 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 20 hom., cov: 32)

Exomes 𝑓: 0.013 ( 147 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.92

Publications

8 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-27342158-C-T is Benign according to our data. Variant chr16-27342158-C-T is described in ClinVar as [Benign]. Clinvar id is 771761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 20 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.108C>T	p.Ser36Ser	synonymous_variant	Exon 4 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.108C>T	p.Ser36Ser	synonymous_variant	Exon 4 of 11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.00999

AC:

1521

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00993

AC:

2497

AN:

251446

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00911

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.0130

AC:

19071

AN:

1461858

Hom.:

147

Cov.:

AF XY:

0.0128

AC XY:

9303

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00263

AC:

AN:

33480

American (AMR)

AF:

0.00912

AC:

408

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

777

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00508

AC:

438

AN:

86254

European-Finnish (FIN)

AF:

0.00256

AC:

137

AN:

53414

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0146

AC:

16289

AN:

1111990

Other (OTH)

AF:

0.0141

AC:

854

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

977

1953

2930

3906

4883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00999

AC:

1522

AN:

152332

Hom.:

Cov.:

AF XY:

0.00990

AC XY:

737

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00334

AC:

139

AN:

41570

American (AMR)

AF:

0.0140

AC:

215

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

114

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00373

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0145

AC:

988

AN:

68026

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0166

EpiControl

AF:

0.0176

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

IL4R-related disorder

Benign:1

Dec 19, 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

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.8

(source)

DANN

Benign

0.64

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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16-27342158-C-T

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