rs2074570

Variant names:

• chr16-27363836-T-C
• rs2074570
• NM_000418.4:c.*6T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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 (no stars).

• 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 no assertion criteria provided B:1
• Conservation: PhyloP100: -0.722
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• IgE responsiveness, atopic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 3059990.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.*6T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.*6T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_000418.4	ENSP00000379111.2

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

GnomAD2 exomes AF: 0.0720 AC: 16779 AN: 233168 AF XY: 0.0666

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 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

African (AFR) AF: 0.198 AC: 6599 AN: 33390

American (AMR) AF: 0.125 AC: 5532 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.0269 AC: 691 AN: 25734

East Asian (EAS) AF: 0.0820 AC: 3252 AN: 39656

South Asian (SAS) AF: 0.0809 AC: 6929 AN: 85640

European-Finnish (FIN) AF: 0.0609 AC: 2454 AN: 40280

Middle Eastern (MID) AF: 0.0323 AC: 185 AN: 5736

European-Non Finnish (NFE) AF: 0.0376 AC: 41701 AN: 1108718

Other (OTH) AF: 0.0523 AC: 3144 AN: 60122

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

African (AFR) AF: 0.186 AC: 7714 AN: 41550

American (AMR) AF: 0.0981 AC: 1501 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.0733 AC: 380 AN: 5182

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4830

European-Finnish (FIN) AF: 0.0702 AC: 746 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2671 AN: 68022

Other (OTH) AF: 0.0733 AC: 155 AN: 2116

Alfa AF: 0.0608 Hom.: 245

Bravo AF: 0.0977

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

IL4R-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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