rs3024678

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000418.4(IL4R):c.2023C>T(p.Pro675Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,158 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 13 hom., cov: 33)

Exomes 𝑓: 0.019 ( 339 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.557

Publications

16 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 (MetaRNN=0.0051090717).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0116 (1772/152314) while in subpopulation NFE AF = 0.0202 (1376/68004). AF 95% confidence interval is 0.0193. There are 13 homozygotes in GnomAd4. There are 744 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 Unknown gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
IL4R	NM_000418.4	MANE Select	c.2023C>T	p.Pro675Ser	missense	Exon 11 of 11	NP_000409.1	P24394-1
IL4R	NM_001257406.2		c.2023C>T	p.Pro675Ser	missense	Exon 10 of 10	NP_001244335.1	P24394-1
IL4R	NM_001257407.2		c.1978C>T	p.Pro660Ser	missense	Exon 11 of 11	NP_001244336.1	P24394-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL4R	ENST00000395762.7	TSL:1 MANE Select	c.2023C>T	p.Pro675Ser	missense	Exon 11 of 11	ENSP00000379111.2	P24394-1
IL4R	ENST00000543915.6	TSL:1	c.2023C>T	p.Pro675Ser	missense	Exon 10 of 10	ENSP00000441667.2	P24394-1
IL4R	ENST00000912076.1		c.2044C>T	p.Pro682Ser	missense	Exon 10 of 10	ENSP00000582135.1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1772

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00371

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0113

AC:

2836

AN:

251080

AF XY:

0.0115

show subpopulations

Gnomad AFR exome

AF:

0.00327

Gnomad AMR exome

AF:

0.00697

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0190

AC:

27796

AN:

1461844

Hom.:

339

Cov.:

AF XY:

0.0185

AC XY:

13443

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00278

AC:

AN:

33480

American (AMR)

AF:

0.00722

AC:

323

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

128

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00508

AC:

438

AN:

86256

European-Finnish (FIN)

AF:

0.00260

AC:

139

AN:

53388

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0230

AC:

25551

AN:

1112004

Other (OTH)

AF:

0.0181

AC:

1095

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1663

3325

4988

6650

8313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

974

1948

2922

3896

4870

<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:

0.0116

AC:

1772

AN:

152314

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

744

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00370

AC:

154

AN:

41578

American (AMR)

AF:

0.0103

AC:

158

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00393

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0202

AC:

1376

AN:

68004

Other (OTH)

AF:

0.0138

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

188

281

375

469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0174

Hom.:

Bravo

AF:

0.0127

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00478

AC:

ESP6500EA

AF:

0.0201

AC:

173

ExAC

AF:

0.0108

AC:

1316

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.56

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.10

Sift

Uncertain

0.0060

Sift4G

Benign

0.38

Polyphen

0.83

Vest4

0.064

MPC

0.16

ClinPred

0.024

GERP RS

3.4

Varity_R

0.063

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(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