Genetic Variant NM_000418.4: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_000418.4:c.900-15C>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