rs2239347

Positions:

• chr16-27347700-A-C

Variant summary

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

The NM_000418.4(IL4R):​c.513+1082A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,874 control chromosomes in the GnomAD database, including 15,698 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 0.45 (15698 hom., cov: 32)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.513+1082A>C		intron_variant		ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.513+1082A>C		intron_variant		1	NM_000418.4	ENSP00000379111	P1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68819 AN: 151756 Hom.: 15665 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68918 AN: 151874 Hom.: 15698 Cov.: 32 AF XY: 0.453 AC XY: 33609 AN XY: 74218

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.465

Alfa AF: 0.459 Hom.: 15898

Bravo AF: 0.460

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.51

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: rs2239347; hg19: chr16-27359021;