rs2234898

chr16-27362594-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000418.4(IL4R):c.1242G>T(p.Leu414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,786 control chromosomes in the GnomAD database, including 21,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (6757 hom., cov: 32)
  • Exomes 𝑓: 0.12 (14624 hom.)
• Consequence: IL4R NM_000418.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-27362594-G-T is Benign according to our data. Variant chr16-27362594-G-T is described in ClinVar as [Benign]. Clinvar id is 3056799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.1242G>T	p.Leu414=	synonymous_variant	11/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.1242G>T	p.Leu414=	synonymous_variant	11/11	1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34695 AN: 151934 Hom.: 6733 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.132 AC: 33227 AN: 251330 Hom.: 3785 AF XY: 0.120 AC XY: 16278 AN XY: 135838

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.0556

Gnomad EAS exome AF: 0.0737

Gnomad SAS exome AF: 0.0559

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.122 AC: 178610 AN: 1461734 Hom.: 14624 Cov.: 35 AF XY: 0.118 AC XY: 85727 AN XY: 727176

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.0563

Gnomad4 EAS exome AF: 0.0685

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.229 AC: 34774 AN: 152052 Hom.: 6757 Cov.: 32 AF XY: 0.223 AC XY: 16581 AN XY: 74358

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0656

Gnomad4 SAS AF: 0.0617

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.198

Alfa AF: 0.137 Hom.: 2862

Bravo AF: 0.247

Asia WGS AF: 0.130 AC: 452 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

IL4R-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.91
Dann	Benign	0.62

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: rs2234898; hg19: chr16-27373915; COSMIC: COSV50138798; COSMIC: COSV50138798;