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rs1805015

Variant summary

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

The NM_000418.4(IL4R):c.1507T>C(p.Ser503Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,858 control chromosomes in the GnomAD database, including 25,776 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4428 hom., cov: 32)
Exomes 𝑓: 0.17 ( 21348 hom. )

Consequence

IL4R
NM_000418.4 missense

Scores

1
16

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 0.124
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 Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.003134787).
BP6
Variant 16-27362859-T-C is Benign according to our data. Variant chr16-27362859-T-C is described in ClinVar as [protective]. Clinvar id is 14667.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL4RNM_000418.4 linkuse as main transcriptc.1507T>C p.Ser503Pro missense_variant 11/11 ENST00000395762.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL4RENST00000395762.7 linkuse as main transcriptc.1507T>C p.Ser503Pro missense_variant 11/111 NM_000418.4 P1P24394-1

Frequencies

GnomAD3 genomes
AF:
0.217
AC:
33005
AN:
151926
Hom.:
4411
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.380
Gnomad AMI
AF:
0.0275
Gnomad AMR
AF:
0.201
Gnomad ASJ
AF:
0.135
Gnomad EAS
AF:
0.0723
Gnomad SAS
AF:
0.0990
Gnomad FIN
AF:
0.125
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.163
Gnomad OTH
AF:
0.205
GnomAD3 exomes
AF:
0.159
AC:
39895
AN:
251224
Hom.:
3702
AF XY:
0.152
AC XY:
20640
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.385
Gnomad AMR exome
AF:
0.161
Gnomad ASJ exome
AF:
0.132
Gnomad EAS exome
AF:
0.0796
Gnomad SAS exome
AF:
0.0968
Gnomad FIN exome
AF:
0.133
Gnomad NFE exome
AF:
0.163
Gnomad OTH exome
AF:
0.156
GnomAD4 exome
AF:
0.165
AC:
241533
AN:
1461814
Hom.:
21348
Cov.:
35
AF XY:
0.162
AC XY:
117745
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.383
Gnomad4 AMR exome
AF:
0.163
Gnomad4 ASJ exome
AF:
0.135
Gnomad4 EAS exome
AF:
0.0715
Gnomad4 SAS exome
AF:
0.101
Gnomad4 FIN exome
AF:
0.138
Gnomad4 NFE exome
AF:
0.169
Gnomad4 OTH exome
AF:
0.170
GnomAD4 genome
AF:
0.217
AC:
33065
AN:
152044
Hom.:
4428
Cov.:
32
AF XY:
0.211
AC XY:
15666
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.380
Gnomad4 AMR
AF:
0.201
Gnomad4 ASJ
AF:
0.135
Gnomad4 EAS
AF:
0.0723
Gnomad4 SAS
AF:
0.0985
Gnomad4 FIN
AF:
0.125
Gnomad4 NFE
AF:
0.163
Gnomad4 OTH
AF:
0.204
Alfa
AF:
0.168
Hom.:
5859
Bravo
AF:
0.227
TwinsUK
AF:
0.170
AC:
630
ALSPAC
AF:
0.173
AC:
668
ESP6500AA
AF:
0.363
AC:
1595
ESP6500EA
AF:
0.162
AC:
1391
ExAC
AF:
0.163
AC:
19843
Asia WGS
AF:
0.131
AC:
456
AN:
3478
EpiCase
AF:
0.155
EpiControl
AF:
0.152

ClinVar

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

Submissions by phenotype

Atopy, resistance to Benign:1
protective, no assertion criteria providedliterature onlyOMIMOct 07, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.62
Cadd
Benign
8.2
Dann
Uncertain
0.99
DEOGEN2
Benign
0.061
T;T;.
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.048
N
MetaRNN
Benign
0.0031
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.2
L;L;.
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.24
N;N;.
REVEL
Benign
0.085
Sift
Benign
0.27
T;T;.
Sift4G
Benign
0.12
T;T;T
Polyphen
0.54
P;P;.
Vest4
0.14
MPC
0.38
ClinPred
0.012
T
GERP RS
1.6
Varity_R
0.095
gMVP
0.20

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: rs1805015; hg19: chr16-27374180; COSMIC: COSV50142827; COSMIC: COSV50142827; API