rs2234897

chr16-27362291-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000418.4(IL4R):c.939T>C(p.Phe313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,614,140 control chromosomes in the GnomAD database, including 557 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 0.019 (37 hom., cov: 32)
  • Exomes 𝑓: 0.024 (520 hom.)
• Consequence: IL4R NM_000418.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-1.36 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2859/152280) while in subpopulation NFE AF= 0.0259 (1760/68028). AF 95% confidence interval is 0.0249. There are 37 homozygotes in gnomad4. There are 1513 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.939T>C	p.Phe313=	synonymous_variant	11/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.939T>C	p.Phe313=	synonymous_variant	11/11	1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2859 AN: 152162 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0580

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0211 AC: 5309 AN: 251416 Hom.: 97 AF XY: 0.0213 AC XY: 2889 AN XY: 135878

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.00827

Gnomad ASJ exome AF: 0.0185

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0152

Gnomad FIN exome AF: 0.0543

Gnomad NFE exome AF: 0.0265

Gnomad OTH exome AF: 0.0191

GnomAD4 exome AF: 0.0240 AC: 35020 AN: 1461860 Hom.: 520 Cov.: 34 AF XY: 0.0237 AC XY: 17263 AN XY: 727232

Gnomad4 AFR exome AF: 0.00367

Gnomad4 AMR exome AF: 0.00892

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.0516

Gnomad4 NFE exome AF: 0.0258

Gnomad4 OTH exome AF: 0.0191

GnomAD4 genome AF: 0.0188 AC: 2859 AN: 152280 Hom.: 37 Cov.: 32 AF XY: 0.0203 AC XY: 1513 AN XY: 74456

Gnomad4 AFR AF: 0.00351

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0580

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0222 Hom.: 53

Bravo AF: 0.0146

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0210

EpiControl AF: 0.0220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.54
Dann	Benign	0.58

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: rs2234897; hg19: chr16-27373612;