16-27363079-A-T

Position:

• chr16-27363079-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000418.4(IL4R):​c.1727A>T​(p.Gln576Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL4R NM_000418.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1476826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.1727A>T	p.Gln576Leu	missense_variant	11/11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.1727A>T	p.Gln576Leu	missense_variant	11/11	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.49	.;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.040
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.18	B;B;.
Vest4		0.23
MutPred		0.43		Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);.;
MVP		0.27
MPC		0.13
ClinPred		0.41	T
GERP RS		2.8
Varity_R		0.071
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

Other links and lift over

dbSNP: rs1801275; hg19: chr16-27374400;