dbSNP rs3024632: IL4R:c.671-833T>C (chr16-27354975-T-C) – 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.671-833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 462,704 control chromosomes in the GnomAD database, including 1,587 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 0.088 ( 659 hom., cov: 32)

Exomes 𝑓: 0.073 ( 928 hom. )

Consequence

IL4R
NM_000418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.536

Publications

8 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.671-833T>C		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.671-833T>C		intron_variant	Intron 7 of 10	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0881

AC:

13407

AN:

152106

Hom.:

656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0643

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0507

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0849

Gnomad OTH

AF:

0.0871

GnomAD2 exomes

AF:

0.0696

AC:

10495

AN:

150796

AF XY:

0.0691

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0409

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.000277

Gnomad FIN exome

AF:

0.0734

Gnomad NFE exome

AF:

0.0851

Gnomad OTH exome

AF:

0.0852

GnomAD4 exome

AF:

0.0728

AC:

22610

AN:

310480

Hom.:

928

Cov.:

AF XY:

0.0705

AC XY:

12280

AN XY:

174082

show subpopulations

African (AFR)

AF:

0.133

AC:

1125

AN:

8488

American (AMR)

AF:

0.0414

AC:

1114

AN:

26920

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

1204

AN:

10634

East Asian (EAS)

AF:

0.000338

AC:

AN:

8874

South Asian (SAS)

AF:

0.0523

AC:

3096

AN:

59238

European-Finnish (FIN)

AF:

0.0724

AC:

2033

AN:

28088

Middle Eastern (MID)

AF:

0.120

AC:

330

AN:

2752

European-Non Finnish (NFE)

AF:

0.0827

AC:

12542

AN:

151574

Other (OTH)

AF:

0.0836

AC:

1163

AN:

13912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

955

1911

2866

3822

4777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0881

AC:

13415

AN:

152224

Hom.:

659

Cov.:

AF XY:

0.0862

AC XY:

6419

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.122

AC:

5046

AN:

41522

American (AMR)

AF:

0.0642

AC:

983

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0505

AC:

244

AN:

4830

European-Finnish (FIN)

AF:

0.0746

AC:

791

AN:

10608

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0849

AC:

5771

AN:

67992

Other (OTH)

AF:

0.0866

AC:

183

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

622

1244

1867

2489

3111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0920

Hom.:

168

Bravo

AF:

0.0891

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.6

(source)

DANN

Benign

0.55

PhyloP100

-0.54

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