rs3024633

Variant names:

• chr16-27355178-A-G
• rs3024633
• NM_000418.4:c.671-630A>G

Variant summary

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

The NM_000418.4(IL4R):​c.671-630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 328,324 control chromosomes in the GnomAD database, including 919 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 0.072 (446 hom., cov: 32)
  • Exomes 𝑓: 0.065 (473 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.671-630A>G		intron_variant	Intron 7 of 10	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.671-630A>G		intron_variant	Intron 7 of 10	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10870 AN: 152080 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0739

GnomAD4 exome AF: 0.0655 AC: 11532 AN: 176126 Hom.: 473 AF XY: 0.0634 AC XY: 6177 AN XY: 97420

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.000299

Gnomad4 SAS exome AF: 0.0493

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.0753

GnomAD4 genome AF: 0.0715 AC: 10883 AN: 152198 Hom.: 446 Cov.: 32 AF XY: 0.0701 AC XY: 5218 AN XY: 74408

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0990

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0735

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0731

Alfa AF: 0.0813 Hom.: 604

Bravo AF: 0.0703

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.50

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: rs3024633; hg19: chr16-27366499;