rs3024613

Positions:

• chr16-27352932-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.670+236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,046 control chromosomes in the GnomAD database, including 14,253 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 0.41 (14253 hom., cov: 32)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95

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 (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.670+236C>T		intron_variant		ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.670+236C>T		intron_variant		1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62036 AN: 151928 Hom.: 14266 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.408 AC: 62014 AN: 152046 Hom.: 14253 Cov.: 32 AF XY: 0.410 AC XY: 30447 AN XY: 74288

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.445

Alfa AF: 0.490 Hom.: 31998

Bravo AF: 0.395

Asia WGS AF: 0.387 AC: 1344 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	0.022
DANN	Benign	0.50

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: rs3024613; hg19: chr16-27364253;