rs3024536

Variant names:

• chr16-27341392-C-T
• rs3024536
• NM_000418.4:c.71-729C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000418.4(IL4R):​c.71-729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 582,936 control chromosomes in the GnomAD database, including 4,944 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 0.12 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3715 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.71-729C>T		intron_variant	Intron 3 of 10	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.71-729C>T		intron_variant	Intron 3 of 10	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 152024 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.124 AC: 53541 AN: 430794 Hom.: 3715 AF XY: 0.124 AC XY: 27944 AN XY: 225436

African (AFR) AF: 0.119 AC: 1445 AN: 12154

American (AMR) AF: 0.0812 AC: 1425 AN: 17542

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 2150 AN: 13430

East Asian (EAS) AF: 0.000364 AC: 11 AN: 30260

South Asian (SAS) AF: 0.0976 AC: 4004 AN: 41032

European-Finnish (FIN) AF: 0.0973 AC: 2823 AN: 29020

Middle Eastern (MID) AF: 0.170 AC: 603 AN: 3554

European-Non Finnish (NFE) AF: 0.146 AC: 37785 AN: 258384

Other (OTH) AF: 0.130 AC: 3295 AN: 25418

GnomAD4 genome AF: 0.120 AC: 18297 AN: 152142 Hom.: 1229 Cov.: 32 AF XY: 0.117 AC XY: 8697 AN XY: 74386

African (AFR) AF: 0.116 AC: 4804 AN: 41500

American (AMR) AF: 0.0914 AC: 1396 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0848 AC: 409 AN: 4822

European-Finnish (FIN) AF: 0.0965 AC: 1021 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9798 AN: 67996

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.140 Hom.: 2117

Bravo AF: 0.119

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.52
PhyloP100		-0.82
PromoterAI		0.0026	Neutral
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: rs3024536; hg19: chr16-27352713;