rs2234895

chr16-27346606-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000418.4(IL4R):c.501C>T(p.Asn167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,613,662 control chromosomes in the GnomAD database, including 5,628 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 0.072 (481 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5147 hom.)
• Consequence: IL4R NM_000418.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.721 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.501C>T	p.Asn167=	synonymous_variant	6/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.501C>T	p.Asn167=	synonymous_variant	6/11	1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10979 AN: 152128 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0765

GnomAD3 exomes AF: 0.0687 AC: 17271 AN: 251266 Hom.: 725 AF XY: 0.0698 AC XY: 9485 AN XY: 135800

Gnomad AFR exome AF: 0.0548

Gnomad AMR exome AF: 0.0379

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0518

Gnomad FIN exome AF: 0.0766

Gnomad NFE exome AF: 0.0893

Gnomad OTH exome AF: 0.0840

GnomAD4 exome AF: 0.0807 AC: 117967 AN: 1461416 Hom.: 5147 Cov.: 32 AF XY: 0.0803 AC XY: 58376 AN XY: 727002

Gnomad4 AFR exome AF: 0.0549

Gnomad4 AMR exome AF: 0.0413

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0525

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0875

Gnomad4 OTH exome AF: 0.0786

GnomAD4 genome AF: 0.0721 AC: 10980 AN: 152246 Hom.: 481 Cov.: 32 AF XY: 0.0703 AC XY: 5234 AN XY: 74444

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0794

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0849 Hom.: 807

Bravo AF: 0.0699

Asia WGS AF: 0.0260 AC: 90 AN: 3478

EpiCase AF: 0.0944

EpiControl AF: 0.0933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	3.0
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2234895; hg19: chr16-27357927;