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rs1801275

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000418.4(IL4R):c.1727A>G(p.Gln576Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,613,910 control chromosomes in the GnomAD database, including 54,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 12743 hom., cov: 33)
Exomes 𝑓: 0.22 ( 41529 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

17

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.1686489E-6).
BP6
Variant 16-27363079-A-G is Benign according to our data. Variant chr16-27363079-A-G is described in ClinVar as [Benign]. Clinvar id is 14665.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL4RNM_000418.4 linkuse as main transcriptc.1727A>G p.Gln576Arg missense_variant 11/11 ENST00000395762.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL4RENST00000395762.7 linkuse as main transcriptc.1727A>G p.Gln576Arg missense_variant 11/111 NM_000418.4 P1P24394-1

Frequencies

GnomAD3 genomes
AF:
0.347
AC:
52747
AN:
152070
Hom.:
12686
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.688
Gnomad AMI
AF:
0.0912
Gnomad AMR
AF:
0.318
Gnomad ASJ
AF:
0.171
Gnomad EAS
AF:
0.155
Gnomad SAS
AF:
0.227
Gnomad FIN
AF:
0.195
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.306
GnomAD3 exomes
AF:
0.248
AC:
61954
AN:
250126
Hom.:
9564
AF XY:
0.235
AC XY:
31920
AN XY:
135542
show subpopulations
Gnomad AFR exome
AF:
0.703
Gnomad AMR exome
AF:
0.300
Gnomad ASJ exome
AF:
0.167
Gnomad EAS exome
AF:
0.166
Gnomad SAS exome
AF:
0.222
Gnomad FIN exome
AF:
0.199
Gnomad NFE exome
AF:
0.206
Gnomad OTH exome
AF:
0.224
GnomAD4 exome
AF:
0.225
AC:
328389
AN:
1461722
Hom.:
41529
Cov.:
36
AF XY:
0.222
AC XY:
161640
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.707
Gnomad4 AMR exome
AF:
0.301
Gnomad4 ASJ exome
AF:
0.169
Gnomad4 EAS exome
AF:
0.159
Gnomad4 SAS exome
AF:
0.224
Gnomad4 FIN exome
AF:
0.200
Gnomad4 NFE exome
AF:
0.211
Gnomad4 OTH exome
AF:
0.240
GnomAD4 genome
AF:
0.347
AC:
52863
AN:
152188
Hom.:
12743
Cov.:
33
AF XY:
0.343
AC XY:
25484
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.688
Gnomad4 AMR
AF:
0.317
Gnomad4 ASJ
AF:
0.171
Gnomad4 EAS
AF:
0.155
Gnomad4 SAS
AF:
0.226
Gnomad4 FIN
AF:
0.195
Gnomad4 NFE
AF:
0.207
Gnomad4 OTH
AF:
0.305
Alfa
AF:
0.226
Hom.:
10956
Bravo
AF:
0.369
TwinsUK
AF:
0.211
AC:
781
ALSPAC
AF:
0.215
AC:
829
ESP6500AA
AF:
0.674
AC:
2963
ESP6500EA
AF:
0.204
AC:
1753
ExAC
AF:
0.254
AC:
30865
Asia WGS
AF:
0.278
AC:
967
AN:
3478
EpiCase
AF:
0.195
EpiControl
AF:
0.189

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Atopy, resistance to Benign:1
Benign, no assertion criteria providedliterature onlyOMIMFeb 01, 2005- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.81
T
BayesDel_noAF
Benign
-0.79
Cadd
Benign
13
Dann
Benign
0.24
DEOGEN2
Benign
0.074
T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.025
N
MetaRNN
Benign
0.0000012
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.5
N;N;.
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Benign
0.38
T
PROVEAN
Benign
0.89
N;N;.
REVEL
Benign
0.065
Sift
Benign
1.0
T;T;.
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.031
MPC
0.14
ClinPred
0.00026
T
GERP RS
2.8
Varity_R
0.018
gMVP
0.14

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: rs1801275; hg19: chr16-27374400; COSMIC: COSV50142227; COSMIC: COSV50142227; API