Genetic Variant IL4R:c.900-15C>A (chr16-27362237-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000418.4(IL4R):c.900-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,609,810 control chromosomes in the GnomAD database, including 35,456 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 9286 hom., cov: 32)

Exomes 𝑓: 0.17 ( 26170 hom. )

Consequence

IL4R
NM_000418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.532

Publications

27 publications found

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 Gene-Disease associations (from GenCC):

IgE responsiveness, atopic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

IL4R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.900-15C>A		intron_variant	Intron 10 of 10	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.900-15C>A		intron_variant	Intron 10 of 10	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42991

AN:

151944

Hom.:

9246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.0995

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.252

GnomAD2 exomes

AF:

0.178

AC:

44425

AN:

249658

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.0792

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.173

AC:

252519

AN:

1457748

Hom.:

26170

Cov.:

AF XY:

0.169

AC XY:

122566

AN XY:

724890

show subpopulations

African (AFR)

AF:

0.627

AC:

20867

AN:

33274

American (AMR)

AF:

0.179

AC:

7973

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3666

AN:

25908

East Asian (EAS)

AF:

0.0713

AC:

2828

AN:

39660

South Asian (SAS)

AF:

0.101

AC:

8721

AN:

85966

European-Finnish (FIN)

AF:

0.138

AC:

7347

AN:

53352

Middle Eastern (MID)

AF:

0.171

AC:

981

AN:

5748

European-Non Finnish (NFE)

AF:

0.170

AC:

188761

AN:

1109208

Other (OTH)

AF:

0.189

AC:

11375

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

9403

18805

28208

37610

47013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.283

AC:

43087

AN:

152062

Hom.:

9286

Cov.:

AF XY:

0.275

AC XY:

20456

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.607

AC:

25145

AN:

41440

American (AMR)

AF:

0.225

AC:

3449

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

490

AN:

3470

East Asian (EAS)

AF:

0.0719

AC:

372

AN:

5176

South Asian (SAS)

AF:

0.0990

AC:

477

AN:

4818

European-Finnish (FIN)

AF:

0.125

AC:

1321

AN:

10570

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11216

AN:

67978

Other (OTH)

AF:

0.252

AC:

532

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1245

2489

3734

4978

6223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.231

Hom.:

3264

Bravo

AF:

0.303

Asia WGS

AF:

0.155

AC:

538

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.3

(source)

DANN

Benign

0.82

PhyloP100

-0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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16-27362237-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over