dbSNP rs3024570: IL4R:c.362-4G>A (chr16-27346463-G-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.362-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,613,560 control chromosomes in the GnomAD database, including 4,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 357 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4395 hom. )

Consequence

IL4R
NM_000418.4 splice_region, intron

Scores

Splicing: ADA: 0.00002553

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70

Publications

14 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.362-4G>A		splice_region_variant, intron_variant	Intron 5 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.362-4G>A		splice_region_variant, intron_variant	Intron 5 of 10	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0578

AC:

8777

AN:

151932

Hom.:

357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0515

Gnomad ASJ

AF:

0.0998

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0473

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.0645

GnomAD2 exomes

AF:

0.0616

AC:

15476

AN:

251182

AF XY:

0.0635

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0735

Gnomad NFE exome

AF:

0.0822

Gnomad OTH exome

AF:

0.0745

GnomAD4 exome

AF:

0.0740

AC:

108127

AN:

1461510

Hom.:

4395

Cov.:

AF XY:

0.0738

AC XY:

53647

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.0186

AC:

622

AN:

33480

American (AMR)

AF:

0.0366

AC:

1638

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2851

AN:

26132

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.0508

AC:

4385

AN:

86254

European-Finnish (FIN)

AF:

0.0713

AC:

3808

AN:

53404

Middle Eastern (MID)

AF:

0.109

AC:

631

AN:

5764

European-Non Finnish (NFE)

AF:

0.0808

AC:

89831

AN:

1111668

Other (OTH)

AF:

0.0720

AC:

4350

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4678

9357

14035

18714

23392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3224

6448

9672

12896

16120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0577

AC:

8773

AN:

152050

Hom.:

357

Cov.:

AF XY:

0.0569

AC XY:

4231

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0214

AC:

886

AN:

41490

American (AMR)

AF:

0.0515

AC:

785

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0998

AC:

346

AN:

3468

East Asian (EAS)

AF:

0.000773

AC:

AN:

5174

South Asian (SAS)

AF:

0.0473

AC:

228

AN:

4818

European-Finnish (FIN)

AF:

0.0759

AC:

801

AN:

10554

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0817

AC:

5553

AN:

67972

Other (OTH)

AF:

0.0639

AC:

135

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

403

806

1208

1611

2014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0723

Hom.:

758

Bravo

AF:

0.0548

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0871

EpiControl

AF:

0.0864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.20

(source)

DANN

Benign

0.36

PhyloP100

-1.7

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0

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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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