Genetic Variant IL4R:c.-151-328A>G (chr16-27329738-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.-151-328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,414 control chromosomes in the GnomAD database, including 7,915 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 0.32 ( 7915 hom., cov: 30)

Consequence

IL4R
NM_000418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.817

Publications

27 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:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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
IL4R	NM_000418.4	MANE Select	c.-151-328A>G	intron	N/A	NP_000409.1
IL4R	NM_001257406.2		c.-18-10448A>G	intron	N/A	NP_001244335.1
IL4R	NM_001257407.2		c.-307-10448A>G	intron	N/A	NP_001244336.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL4R	ENST00000395762.7	TSL:1 MANE Select	c.-151-328A>G	intron	N/A	ENSP00000379111.2
IL4R	ENST00000543915.6	TSL:1	c.-18-10448A>G	intron	N/A	ENSP00000441667.2
IL4R	ENST00000563002.5	TSL:5	c.-18-10448A>G	intron	N/A	ENSP00000456930.1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48023

AN:

151296

Hom.:

7906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.318

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.318

AC:

48080

AN:

151414

Hom.:

7915

Cov.:

AF XY:

0.317

AC XY:

23445

AN XY:

73918

show subpopulations

African (AFR)

AF:

0.331

AC:

13649

AN:

41232

American (AMR)

AF:

0.336

AC:

5097

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

829

AN:

3472

East Asian (EAS)

AF:

0.513

AC:

2639

AN:

5140

South Asian (SAS)

AF:

0.349

AC:

1679

AN:

4812

European-Finnish (FIN)

AF:

0.257

AC:

2679

AN:

10408

Middle Eastern (MID)

AF:

0.271

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.299

AC:

20282

AN:

67886

Other (OTH)

AF:

0.321

AC:

676

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1614

3228

4841

6455

8069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.305

Hom.:

12167

Bravo

AF:

0.326

Asia WGS

AF:

0.403

AC:

1404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.38

(source)

DANN

Benign

0.79

PhyloP100

-0.82

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over