dbSNP rs2234898: IL4R:p.Leu414Leu (chr16-27362594-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000418.4(IL4R):c.1242G>T(p.Leu414Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,786 control chromosomes in the GnomAD database, including 21,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 6757 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14624 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.198

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-27362594-G-T is Benign according to our data. Variant chr16-27362594-G-T is described in ClinVar as [Benign]. Clinvar id is 3056799.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.198 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.1242G>T	p.Leu414Leu	synonymous_variant	Exon 11 of 11	ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 link	c.1242G>T	p.Leu414Leu	synonymous_variant	Exon 11 of 11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34695

AN:

151934

Hom.:

6733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.0656

Gnomad SAS

AF:

0.0621

Gnomad FIN

AF:

0.0953

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.132

AC:

33227

AN:

251330

Hom.:

3785

AF XY:

0.120

AC XY:

16278

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.0556

Gnomad EAS exome

AF:

0.0737

Gnomad SAS exome

AF:

0.0559

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.122

AC:

178610

AN:

1461734

Hom.:

14624

Cov.:

AF XY:

0.118

AC XY:

85727

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.550

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.0563

Gnomad4 EAS exome

AF:

0.0685

Gnomad4 SAS exome

AF:

0.0584

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.229

AC:

34774

AN:

152052

Hom.:

6757

Cov.:

AF XY:

0.223

AC XY:

16581

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.532

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.0542

Gnomad4 EAS

AF:

0.0656

Gnomad4 SAS

AF:

0.0617

Gnomad4 FIN

AF:

0.0953

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.137

Hom.:

2862

Bravo

AF:

0.247

Asia WGS

AF:

0.130

AC:

452

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL4R-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.71

CADD

Benign

0.91

DANN

Benign

0.62

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