rs3024570

Positions:

• chr16-27346463-G-A
• chr16-27346463-G-T

Variant summary

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

The NM_000418.4(IL4R):​c.362-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,613,560 control chromosomes in the GnomAD database, including 4,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (357 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4395 hom.)
• Consequence: IL4R NM_000418.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002553
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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]

IL4R (HGNC:):

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 = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.362-4G>A		splice_region_variant, intron_variant		ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.362-4G>A		splice_region_variant, intron_variant		1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8777 AN: 151932 Hom.: 357 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0645

GnomAD3 exomes AF: 0.0616 AC: 15476 AN: 251182 Hom.: 611 AF XY: 0.0635 AC XY: 8624 AN XY: 135774

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0501

Gnomad FIN exome AF: 0.0735

Gnomad NFE exome AF: 0.0822

Gnomad OTH exome AF: 0.0745

GnomAD4 exome AF: 0.0740 AC: 108127 AN: 1461510 Hom.: 4395 Cov.: 32 AF XY: 0.0738 AC XY: 53647 AN XY: 727084

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.0366

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0508

Gnomad4 FIN exome AF: 0.0713

Gnomad4 NFE exome AF: 0.0808

Gnomad4 OTH exome AF: 0.0720

GnomAD4 genome AF: 0.0577 AC: 8773 AN: 152050 Hom.: 357 Cov.: 32 AF XY: 0.0569 AC XY: 4231 AN XY: 74324

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0817

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0737 Hom.: 648

Bravo AF: 0.0548

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.0871

EpiControl AF: 0.0864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.36
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0
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: rs3024570; hg19: chr16-27357784;