Variant rs2074570 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.*6T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,596,006 control chromosomes in the GnomAD database, including 3,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.090 ( 917 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2468 hom. )

Consequence

IL4R
NM_000418.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.722

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-27363836-T-C is Benign according to our data. Variant chr16-27363836-T-C is described in ClinVar as [Benign]. Clinvar id is 3059990.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 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.*6T>C		3_prime_UTR_variant	11/11	ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 linkuse as main transcript	c.*6T>C		3_prime_UTR_variant	11/11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0900

AC:

13692

AN:

152188

Hom.:

912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0981

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.0730

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0702

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0735

GnomAD3 exomes

AF:

0.0720

AC:

16779

AN:

233168

Hom.:

872

AF XY:

0.0666

AC XY:

8467

AN XY:

127100

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.0753

Gnomad SAS exome

AF:

0.0824

Gnomad FIN exome

AF:

0.0664

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0558

GnomAD4 exome

AF:

0.0488

AC:

70487

AN:

1443700

Hom.:

2468

Cov.:

AF XY:

0.0492

AC XY:

35306

AN XY:

718132

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.0269

Gnomad4 EAS exome

AF:

0.0820

Gnomad4 SAS exome

AF:

0.0809

Gnomad4 FIN exome

AF:

0.0609

Gnomad4 NFE exome

AF:

0.0376

Gnomad4 OTH exome

AF:

0.0523

GnomAD4 genome

AF:

0.0901

AC:

13720

AN:

152306

Hom.:

917

Cov.:

AF XY:

0.0921

AC XY:

6860

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.0733

Gnomad4 SAS

AF:

0.0816

Gnomad4 FIN

AF:

0.0702

Gnomad4 NFE

AF:

0.0393

Gnomad4 OTH

AF:

0.0733

Alfa

AF:

0.0576

Hom.:

147

Bravo

AF:

0.0977

Asia WGS

AF:

0.0960

AC:

332

AN:

3478

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

Oct 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

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

DANN

Benign

0.56

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