Genetic Variant NM_000418.4:c.*1066A>G (chr16-27364896-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.*1066A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,070 control chromosomes in the GnomAD database, including 20,411 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 0.49 ( 20405 hom., cov: 32)

Exomes 𝑓: 0.50 ( 6 hom. )

Consequence

IL4R
NM_000418.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

17 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.*1066A>G		downstream_gene_variant		ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
IL4R	ENST00000395762.7 link	c.*1066A>G	downstream_gene_variant	1	NM_000418.4	ENSP00000379111.2	P24394-1
IL4R	ENST00000543915.6 link	c.*1066A>G	downstream_gene_variant	1		ENSP00000441667.2	P24394-1
IL4R	ENST00000170630.6 link	c.*1066A>G	downstream_gene_variant	5		ENSP00000170630.3	P24394-3

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74946

AN:

151906

Hom.:

20412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.540

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.528

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.464

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.493

AC:

74950

AN:

152024

Hom.:

20405

Cov.:

AF XY:

0.495

AC XY:

36758

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.237

AC:

9829

AN:

41470

American (AMR)

AF:

0.567

AC:

8662

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2150

AN:

3468

East Asian (EAS)

AF:

0.473

AC:

2450

AN:

5176

South Asian (SAS)

AF:

0.562

AC:

2708

AN:

4818

European-Finnish (FIN)

AF:

0.606

AC:

6394

AN:

10548

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41130

AN:

67952

Other (OTH)

AF:

0.536

AC:

1134

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1817

3634

5452

7269

9086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.549

Hom.:

39027

Bravo

AF:

0.478

Asia WGS

AF:

0.505

AC:

1753

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

(source)

DANN

Benign

0.44

PhyloP100

-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_000418.4:c.*1066A>G

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