16-27364896-A-G

Variant names:

• chr16-27364896-A-G
• rs1029489
• NM_000418.4:c.*1066A>G

Variant summary

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

The NM_000418.4(IL4R):​c.*1066A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,070 control chromosomes in the GnomAD database, including 20,411 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 0.49 (20405 hom., cov: 32)
  • Exomes 𝑓: 0.50 (6 hom.)
• Consequence: IL4R NM_000418.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.*1066A>G		downstream_gene_variant		ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.*1066A>G		downstream_gene_variant		1	NM_000418.4	ENSP00000379111.2
IL4R	ENST00000543915.6	c.*1066A>G		downstream_gene_variant		1		ENSP00000441667.2
IL4R	ENST00000170630.6	c.*1066A>G		downstream_gene_variant		5		ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74946 AN: 151906 Hom.: 20412 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.500 AC: 23 AN: 46 Hom.: 6 AF XY: 0.528 AC XY: 19 AN XY: 36

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.493 AC: 74950 AN: 152024 Hom.: 20405 Cov.: 32 AF XY: 0.495 AC XY: 36758 AN XY: 74294

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.536

Alfa AF: 0.529 Hom.: 3310

Bravo AF: 0.478

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1029489; hg19: chr16-27376217;