rs3024543

Positions:

• chr16-27341909-G-A
• chr16-27341909-G-C

Variant summary

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

The NM_000418.4(IL4R):​c.71-212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 547,260 control chromosomes in the GnomAD database, including 5,103 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 0.14 (1645 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3458 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.71-212G>A		intron_variant		ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.71-212G>A		intron_variant		1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21092 AN: 152084 Hom.: 1642 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.124 AC: 48949 AN: 395058 Hom.: 3458 AF XY: 0.123 AC XY: 25316 AN XY: 205678

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0825

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.000321

Gnomad4 SAS exome AF: 0.0904

Gnomad4 FIN exome AF: 0.0949

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.139 AC: 21123 AN: 152202 Hom.: 1645 Cov.: 32 AF XY: 0.135 AC XY: 10065 AN XY: 74418

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0988

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.141

Alfa AF: 0.0812 Hom.: 126

Bravo AF: 0.141

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.68

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: rs3024543; hg19: chr16-27353230;