rs3024536

Positions:

• chr16-27341392-C-T

Variant summary

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

The NM_000418.4(IL4R):​c.71-729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 582,936 control chromosomes in the GnomAD database, including 4,944 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 0.12 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3715 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.71-729C>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.71-729C>T		intron_variant		1	NM_000418.4	ENSP00000379111	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 152024 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.124 AC: 53541 AN: 430794 Hom.: 3715 AF XY: 0.124 AC XY: 27944 AN XY: 225436

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.000364

Gnomad4 SAS exome AF: 0.0976

Gnomad4 FIN exome AF: 0.0973

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.120 AC: 18297 AN: 152142 Hom.: 1229 Cov.: 32 AF XY: 0.117 AC XY: 8697 AN XY: 74386

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0914

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.129

Alfa AF: 0.141 Hom.: 1760

Bravo AF: 0.119

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.52

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: rs3024536; hg19: chr16-27352713;