rs3024560

Positions:

• chr16-27345346-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000418.4(IL4R):​c.361+326T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 438,880 control chromosomes in the GnomAD database, including 31,402 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 0.38 (10975 hom., cov: 31)
  • Exomes 𝑓: 0.37 (20427 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.361+326T>G		intron_variant		ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.361+326T>G		intron_variant		1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57019 AN: 151826 Hom.: 10957 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.374 AC: 107314 AN: 286936 Hom.: 20427 Cov.: 0 AF XY: 0.377 AC XY: 58768 AN XY: 155780

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.376 AC: 57095 AN: 151944 Hom.: 10975 Cov.: 31 AF XY: 0.373 AC XY: 27737 AN XY: 74298

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.379

Alfa AF: 0.360 Hom.: 13712

Bravo AF: 0.385

Asia WGS AF: 0.438 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.47

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: rs3024560; hg19: chr16-27356667; COSMIC: COSV50166073; COSMIC: COSV50166073;