Variant rs2234900 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.1299T>C(p.Leu433Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,492 control chromosomes in the GnomAD database, including 24,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.25 ( 7921 hom., cov: 31)

Exomes 𝑓: 0.13 ( 16829 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.16

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=-0.91).

BP6

Variant 16-27362651-T-C is Benign according to our data. Variant chr16-27362651-T-C is described in ClinVar as [Benign]. Clinvar id is 3056761.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 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.1299T>C	p.Leu433Leu	synonymous_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.1299T>C	p.Leu433Leu	synonymous_variant	11/11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37440

AN:

151748

Hom.:

7880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.578

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.0714

Gnomad SAS

AF:

0.0645

Gnomad FIN

AF:

0.0965

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.142

AC:

35650

AN:

250978

Hom.:

4389

AF XY:

0.129

AC XY:

17491

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.594

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.0685

Gnomad EAS exome

AF:

0.0792

Gnomad SAS exome

AF:

0.0587

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.131

AC:

190891

AN:

1461626

Hom.:

16829

Cov.:

AF XY:

0.126

AC XY:

91679

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.599

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.0689

Gnomad4 EAS exome

AF:

0.0711

Gnomad4 SAS exome

AF:

0.0613

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.247

AC:

37540

AN:

151866

Hom.:

7921

Cov.:

AF XY:

0.240

AC XY:

17854

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.579

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.0714

Gnomad4 SAS

AF:

0.0640

Gnomad4 FIN

AF:

0.0965

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.148

Hom.:

3493

Bravo

AF:

0.268

Asia WGS

AF:

0.137

AC:

475

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.113

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 28, 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

-0.91

CADD

Benign

0.27

DANN

Benign

0.45

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