Genetic Variant IL4R:c.670+1436C>G (chr16-27354132-C-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.670+1436C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,172 control chromosomes in the GnomAD database, including 8,294 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 ( 8291 hom., cov: 32)

Exomes 𝑓: 0.42 ( 3 hom. )

Consequence

IL4R
NM_000418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.337

Publications

25 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 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.670+1436C>G	intron	N/A	NP_000409.1	P24394-1
IL4R	NM_001257406.2		c.670+1436C>G	intron	N/A	NP_001244335.1	P24394-1
IL4R	NM_001257407.2		c.625+1436C>G	intron	N/A	NP_001244336.1	P24394-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL4R	ENST00000395762.7	TSL:1 MANE Select	c.670+1436C>G	intron	N/A	ENSP00000379111.2	P24394-1
IL4R	ENST00000543915.6	TSL:1	c.670+1436C>G	intron	N/A	ENSP00000441667.2	P24394-1
IL4R	ENST00000912076.1		c.691+1436C>G	intron	N/A	ENSP00000582135.1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48546

AN:

152030

Hom.:

8280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.417

AC:

AN:

Hom.:

Cov.:

AF XY:

0.583

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.319

AC:

48587

AN:

152148

Hom.:

8291

Cov.:

AF XY:

0.323

AC XY:

24007

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.203

AC:

8427

AN:

41514

American (AMR)

AF:

0.385

AC:

5891

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

938

AN:

3470

East Asian (EAS)

AF:

0.467

AC:

2417

AN:

5172

South Asian (SAS)

AF:

0.464

AC:

2242

AN:

4830

European-Finnish (FIN)

AF:

0.329

AC:

3472

AN:

10564

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.352

AC:

23927

AN:

67996

Other (OTH)

AF:

0.322

AC:

681

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1705

3410

5114

6819

8524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.209

Hom.:

514

Bravo

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.0

(source)

DANN

Benign

0.63

PhyloP100

0.34

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