dbSNP rs8832: IL4R:c.*636A>G (chr16-27364466-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.*636A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,200 control chromosomes in the GnomAD database, including 18,021 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 0.46 ( 17994 hom., cov: 32)

Exomes 𝑓: 0.49 ( 27 hom. )

Consequence

IL4R
NM_000418.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.691

Publications

55 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.*636A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
IL4R	ENST00000395762.7 link	c.*636A>G	3_prime_UTR_variant	Exon 11 of 11	1	NM_000418.4	ENSP00000379111.2
IL4R	ENST00000543915.6 link	c.*636A>G	3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000441667.2
IL4R	ENST00000170630.6 link	c.*636A>G	3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000170630.3
IL4R	ENST00000565352.1 link	c.*191A>G	downstream_gene_variant		5		ENSP00000461268.1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70355

AN:

151866

Hom.:

18001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.502

GnomAD4 exome

AF:

0.486

AC:

105

AN:

216

Hom.:

Cov.:

AF XY:

0.541

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.333

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

158

Other (OTH)

AF:

0.389

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.463

AC:

70361

AN:

151984

Hom.:

17994

Cov.:

AF XY:

0.468

AC XY:

34757

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.226

AC:

9352

AN:

41454

American (AMR)

AF:

0.537

AC:

8202

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2041

AN:

3470

East Asian (EAS)

AF:

0.477

AC:

2465

AN:

5168

South Asian (SAS)

AF:

0.559

AC:

2696

AN:

4826

European-Finnish (FIN)

AF:

0.600

AC:

6328

AN:

10550

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37739

AN:

67940

Other (OTH)

AF:

0.499

AC:

1053

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1806

3612

5417

7223

9029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.517

Hom.:

60252

Bravo

AF:

0.447

Asia WGS

AF:

0.499

AC:

1734

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.22

(source)

DANN

Benign

0.37

PhyloP100

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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