Variant 16-27342158-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000418.4(IL4R):c.108C>T(p.Ser36=) 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

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 -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 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant	4/11	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.108C>T	p.Ser36=	synonymous_variant	4/11	1	NM_000418.4	ENSP00000379111	P1	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

GnomAD3 exomes

AF:

0.00993

AC:

2497

AN:

251446

Hom.:

AF XY:

0.0103

AC XY:

1394

AN XY:

135900

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 SAS exome

AF:

0.00493

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

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.00912

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00508

Gnomad4 FIN exome

AF:

0.00256

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.00999

AC:

1522

AN:

152332

Hom.:

Cov.:

AF XY:

0.00990

AC XY:

737

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.0140

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0145

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0129

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

IL4R-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 19, 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

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.8

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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