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GeneBe

rs1805010

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000418.4(IL4R):c.223A>C(p.Ile75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I75V) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

IL4R
NM_000418.4 missense

Scores

2
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.221
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06748855).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL4RNM_000418.4 linkuse as main transcriptc.223A>C p.Ile75Leu missense_variant 5/11 ENST00000395762.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL4RENST00000395762.7 linkuse as main transcriptc.223A>C p.Ile75Leu missense_variant 5/111 NM_000418.4 P1P24394-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
48
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
Cadd
Benign
4.1
Dann
Benign
0.92
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.17
N
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.067
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.8
N;N;N;N;.
Sift
Uncertain
0.020
D;D;D;D;.
Sift4G
Uncertain
0.056
T;T;T;T;T
Polyphen
0.0010
.;B;B;.;.
Vest4
0.14, 0.15, 0.15
MutPred
0.11
Gain of catalytic residue at I75 (P = 0.0017);Gain of catalytic residue at I75 (P = 0.0017);Gain of catalytic residue at I75 (P = 0.0017);Gain of catalytic residue at I75 (P = 0.0017);.;
MVP
0.11
MPC
0.13
ClinPred
0.046
T
GERP RS
0.17
Varity_R
0.30
gMVP
0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1805010; hg19: chr16-27356203; API