rs2074570

Positions:

• chr16-27363836-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000418.4(IL4R):​c.*6T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,596,006 control chromosomes in the GnomAD database, including 3,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (917 hom., cov: 33)
  • Exomes 𝑓: 0.049 (2468 hom.)
• Consequence: IL4R NM_000418.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.722

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-27363836-T-C is Benign according to our data. Variant chr16-27363836-T-C is described in ClinVar as [Benign]. Clinvar id is 3059990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.*6T>C		3_prime_UTR_variant	11/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.*6T>C		3_prime_UTR_variant	11/11	1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13692 AN: 152188 Hom.: 912 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0735

GnomAD3 exomes AF: 0.0720 AC: 16779 AN: 233168 Hom.: 872 AF XY: 0.0666 AC XY: 8467 AN XY: 127100

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.0753

Gnomad SAS exome AF: 0.0824

Gnomad FIN exome AF: 0.0664

Gnomad NFE exome AF: 0.0395

Gnomad OTH exome AF: 0.0558

GnomAD4 exome AF: 0.0488 AC: 70487 AN: 1443700 Hom.: 2468 Cov.: 33 AF XY: 0.0492 AC XY: 35306 AN XY: 718132

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0269

Gnomad4 EAS exome AF: 0.0820

Gnomad4 SAS exome AF: 0.0809

Gnomad4 FIN exome AF: 0.0609

Gnomad4 NFE exome AF: 0.0376

Gnomad4 OTH exome AF: 0.0523

GnomAD4 genome AF: 0.0901 AC: 13720 AN: 152306 Hom.: 917 Cov.: 33 AF XY: 0.0921 AC XY: 6860 AN XY: 74472

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.0733

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.0702

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0576 Hom.: 147

Bravo AF: 0.0977

Asia WGS AF: 0.0960 AC: 332 AN: 3478

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 21, 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	-0.86
CADD	Benign	0.14
DANN	Benign	0.56

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: rs2074570; hg19: chr16-27375157; COSMIC: COSV50145726; COSMIC: COSV50145726;