dbSNP rs2074570: IL4R:c.*6T>C (chr16-27363836-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000418.4(IL4R):c.*6T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,596,006 control chromosomes in the GnomAD database, including 3,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.090 ( 917 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2468 hom. )

Consequence

IL4R
NM_000418.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.722

Publications

19 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-27363836-T-C is Benign according to our data. Variant chr16-27363836-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059990.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL4R	NM_000418.4	MANE Select	c.*6T>C	3_prime_UTR	Exon 11 of 11	NP_000409.1	P24394-1
IL4R	NM_001257406.2		c.*6T>C	3_prime_UTR	Exon 10 of 10	NP_001244335.1	P24394-1
IL4R	NM_001257407.2		c.*6T>C	3_prime_UTR	Exon 11 of 11	NP_001244336.1	P24394-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL4R	ENST00000395762.7	TSL:1 MANE Select	c.*6T>C	3_prime_UTR	Exon 11 of 11	ENSP00000379111.2	P24394-1
IL4R	ENST00000543915.6	TSL:1	c.*6T>C	3_prime_UTR	Exon 10 of 10	ENSP00000441667.2	P24394-1
IL4R	ENST00000912076.1		c.*6T>C	3_prime_UTR	Exon 10 of 10	ENSP00000582135.1

Frequencies

GnomAD3 genomes

AF:

0.0900

AC:

13692

AN:

152188

Hom.:

912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0981

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.0730

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0702

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0735

GnomAD2 exomes

AF:

0.0720

AC:

16779

AN:

233168

AF XY:

0.0666

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.0753

Gnomad FIN exome

AF:

0.0664

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0558

GnomAD4 exome

AF:

0.0488

AC:

70487

AN:

1443700

Hom.:

2468

Cov.:

AF XY:

0.0492

AC XY:

35306

AN XY:

718132

show subpopulations

African (AFR)

AF:

0.198

AC:

6599

AN:

33390

American (AMR)

AF:

0.125

AC:

5532

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.0269

AC:

691

AN:

25734

East Asian (EAS)

AF:

0.0820

AC:

3252

AN:

39656

South Asian (SAS)

AF:

0.0809

AC:

6929

AN:

85640

European-Finnish (FIN)

AF:

0.0609

AC:

2454

AN:

40280

Middle Eastern (MID)

AF:

0.0323

AC:

185

AN:

5736

European-Non Finnish (NFE)

AF:

0.0376

AC:

41701

AN:

1108718

Other (OTH)

AF:

0.0523

AC:

3144

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

3499

6997

10496

13994

17493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1760

3520

5280

7040

8800

<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:

0.0901

AC:

13720

AN:

152306

Hom.:

917

Cov.:

AF XY:

0.0921

AC XY:

6860

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.186

AC:

7714

AN:

41550

American (AMR)

AF:

0.0981

AC:

1501

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3472

East Asian (EAS)

AF:

0.0733

AC:

380

AN:

5182

South Asian (SAS)

AF:

0.0816

AC:

394

AN:

4830

European-Finnish (FIN)

AF:

0.0702

AC:

746

AN:

10620

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0393

AC:

2671

AN:

68022

Other (OTH)

AF:

0.0733

AC:

155

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

629

1257

1886

2514

3143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0608

Hom.:

245

Bravo

AF:

0.0977

Asia WGS

AF:

0.0960

AC:

332

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

IL4R-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

(source)

DANN

Benign

0.56

PhyloP100

-0.72

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over