16-27342184-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000418.4(IL4R):c.134A>G(p.Glu45Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E45K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL4R NM_000418.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.134A>G	p.Glu45Gly	missense_variant	4/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.134A>G	p.Glu45Gly	missense_variant	4/11	1	NM_000418.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

IgE responsiveness, atopic Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Feb 07, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	0.088
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.74	D;D;D;D;D;D
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	0.74	N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.7	D;D;D;D;D;.
Sift	Uncertain	0.0040	D;D;D;D;D;.
Sift4G	Uncertain	0.0090	D;D;D;D;D;D
Polyphen		1.0	.;D;.;D;.;.
Vest4		0.45, 0.45
MutPred		0.77		Loss of catalytic residue at E45 (P = 0.0341);Loss of catalytic residue at E45 (P = 0.0341);Loss of catalytic residue at E45 (P = 0.0341);Loss of catalytic residue at E45 (P = 0.0341);Loss of catalytic residue at E45 (P = 0.0341);.;
MVP		0.41
MPC		0.60
ClinPred		0.92	D
GERP RS		2.5
Varity_R		0.15
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-27353505;