Variant 16-27344882-A-G 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.223A>G(p.Ile75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,613,710 control chromosomes in the GnomAD database, including 166,267 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I75F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.46 ( 15980 hom., cov: 33)

Exomes 𝑓: 0.45 ( 150287 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.221

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=2.4071336E-4).

BP6

Variant 16-27344882-A-G is Benign according to our data. Variant chr16-27344882-A-G is described in ClinVar as [Benign]. Clinvar id is 14666.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-27344882-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4 linkuse as main transcript	c.223A>G	p.Ile75Val	missense_variant	5/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7 linkuse as main transcript	c.223A>G	p.Ile75Val	missense_variant	5/11	1	NM_000418.4	P1	P24394-1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69336

AN:

152006

Hom.:

15955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.466

GnomAD3 exomes

AF:

0.448

AC:

112362

AN:

250934

Hom.:

25389

AF XY:

0.447

AC XY:

60648

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.452

GnomAD4 exome

AF:

0.452

AC:

660298

AN:

1461586

Hom.:

150287

Cov.:

AF XY:

0.452

AC XY:

328928

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.496

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.564

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.452

Gnomad4 OTH exome

AF:

0.455

GnomAD4 genome

AF:

0.456

AC:

69416

AN:

152124

Hom.:

15980

Cov.:

AF XY:

0.451

AC XY:

33541

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.434

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.439

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.468

Alfa

AF:

0.453

Hom.:

33548

Bravo

AF:

0.465

TwinsUK

AF:

0.451

AC:

1671

ALSPAC

AF:

0.452

AC:

1741

ESP6500AA

AF:

0.498

AC:

2189

ESP6500EA

AF:

0.448

AC:

3853

ExAC

AF:

0.451

AC:

54701

Asia WGS

AF:

0.460

AC:

1600

AN:

3478

EpiCase

AF:

0.456

EpiControl

AF:

0.453

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RECLASSIFIED - POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Oct 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.14

DANN

Benign

0.58

DEOGEN2

Benign

0.036

.;T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.28

.;.;T;T;T

MetaRNN

Benign

0.00024

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

0.34

N;N;N;N;.

REVEL

Benign

0.027

Sift

Benign

1.0

T;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;B;B;.;.

Vest4

0.015, 0.014

MPC

0.10

ClinPred

0.0030

GERP RS

0.17

Varity_R

0.065

gMVP

0.21

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