chr16-27358957-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000418.4(IL4R):c.812G>A(p.Arg271His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,613,870 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 5 hom. )
Consequence
IL4R
NM_000418.4 missense
NM_000418.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.687
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004656285).
BP6
?
Variant 16-27358957-G-A is Benign according to our data. Variant chr16-27358957-G-A is described in ClinVar as [Benign]. Clinvar id is 708028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL4R | NM_000418.4 | c.812G>A | p.Arg271His | missense_variant | 9/11 | ENST00000395762.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL4R | ENST00000395762.7 | c.812G>A | p.Arg271His | missense_variant | 9/11 | 1 | NM_000418.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00231 AC: 352AN: 152196Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00232 AC: 584AN: 251444Hom.: 2 AF XY: 0.00241 AC XY: 328AN XY: 135898
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GnomAD4 exome AF: 0.00274 AC: 4005AN: 1461556Hom.: 5 Cov.: 30 AF XY: 0.00278 AC XY: 2019AN XY: 727092
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GnomAD4 genome ? AF: 0.00231 AC: 352AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.00228 AC XY: 170AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2017 | - - |
IL4R-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 20, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;.
REVEL
Benign
Sift
Benign
T;T;.;.
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at