rs4787423

Positions:

• chr16-27356013-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395762.7(IL4R):​c.770+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 705,110 control chromosomes in the GnomAD database, including 258,556 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50607 hom., cov: 29)
  • Exomes 𝑓: 0.87 (207949 hom.)
• Consequence: IL4R ENST00000395762.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.770+106C>T		intron_variant		ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.770+106C>T		intron_variant		1	NM_000418.4	ENSP00000379111	P1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 122897 AN: 151616 Hom.: 50569 Cov.: 29

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.866 AC: 479169 AN: 553376 Hom.: 207949 AF XY: 0.868 AC XY: 258215 AN XY: 297324

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.864

Gnomad4 OTH exome AF: 0.853

GnomAD4 genome AF: 0.811 AC: 122988 AN: 151734 Hom.: 50607 Cov.: 29 AF XY: 0.813 AC XY: 60268 AN XY: 74102

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.840

Alfa AF: 0.856 Hom.: 89451

Bravo AF: 0.807

Asia WGS AF: 0.877 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.53

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: rs4787423; hg19: chr16-27367334;