dbSNP rs3024633: IL4R:c.671-630A>G (chr16-27355178-A-G) – 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.671-630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 328,324 control chromosomes in the GnomAD database, including 919 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 0.072 ( 446 hom., cov: 32)

Exomes 𝑓: 0.065 ( 473 hom. )

Consequence

IL4R
NM_000418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.587

Publications

9 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.671-630A>G		intron_variant	Intron 7 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.671-630A>G		intron_variant	Intron 7 of 10	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0715

AC:

10870

AN:

152080

Hom.:

445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0573

Gnomad ASJ

AF:

0.0990

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.0735

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0835

Gnomad OTH

AF:

0.0739

GnomAD4 exome

AF:

0.0655

AC:

11532

AN:

176126

Hom.:

473

AF XY:

0.0634

AC XY:

6177

AN XY:

97420

show subpopulations

African (AFR)

AF:

0.0670

AC:

319

AN:

4762

American (AMR)

AF:

0.0396

AC:

546

AN:

13802

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

439

AN:

4266

East Asian (EAS)

AF:

0.000299

AC:

AN:

6698

South Asian (SAS)

AF:

0.0493

AC:

1850

AN:

37540

European-Finnish (FIN)

AF:

0.0650

AC:

1053

AN:

16212

Middle Eastern (MID)

AF:

0.107

AC:

224

AN:

2100

European-Non Finnish (NFE)

AF:

0.0785

AC:

6513

AN:

82964

Other (OTH)

AF:

0.0753

AC:

586

AN:

7782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

518

1035

1553

2070

2588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0715

AC:

10883

AN:

152198

Hom.:

446

Cov.:

AF XY:

0.0701

AC XY:

5218

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0668

AC:

2772

AN:

41520

American (AMR)

AF:

0.0573

AC:

875

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0990

AC:

343

AN:

3464

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0499

AC:

241

AN:

4828

European-Finnish (FIN)

AF:

0.0735

AC:

778

AN:

10590

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0835

AC:

5678

AN:

68014

Other (OTH)

AF:

0.0731

AC:

154

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

506

1012

1517

2023

2529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0810

Hom.:

835

Bravo

AF:

0.0703

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

(source)

DANN

Benign

0.50

PhyloP100

0.59

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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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