Variant 16-27344903-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000418.4(IL4R):c.244G>A(p.Ala82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,614,220 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0091 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 275 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.73

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=0.0023322105).

BP6

Variant 16-27344903-G-A is Benign according to our data. Variant chr16-27344903-G-A is described in ClinVar as [Benign]. Clinvar id is 3043783.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0091 (1387/152368) while in subpopulation EAS AF= 0.0433 (225/5192). AF 95% confidence interval is 0.0387. There are 46 homozygotes in gnomad4. There are 937 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.244G>A	p.Ala82Thr	missense_variant	5/11	ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 link	c.244G>A	p.Ala82Thr	missense_variant	5/11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.00911

AC:

1387

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0432

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0850

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0127

AC:

3191

AN:

251248

Hom.:

113

AF XY:

0.0119

AC XY:

1617

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0371

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.0863

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.00555

AC:

8107

AN:

1461852

Hom.:

275

Cov.:

AF XY:

0.00541

AC XY:

3934

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0506

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.0836

Gnomad4 NFE exome

AF:

0.000796

Gnomad4 OTH exome

AF:

0.00528

GnomAD4 genome

AF:

0.00910

AC:

1387

AN:

152368

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

937

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0433

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.0850

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00299

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0111

AC:

1342

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

Aug 21, 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

0.068

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0020

DANN

Benign

0.50

DEOGEN2

Benign

0.030

.;T;T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.56

.;.;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

0.020

N;N;N;N;.

REVEL

Benign

0.014

Sift

Benign

0.81

T;T;T;T;.

Sift4G

Benign

0.19

T;T;T;T;T

Polyphen

0.13

.;B;B;.;.

Vest4

0.027, 0.030, 0.018

MPC

0.12

ClinPred

0.00097

GERP RS

-5.4

Varity_R

0.055

gMVP

0.28

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