16-27360628-A-G

Position:

• chr16-27360628-A-G

Variant summary

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

The ENST00000395762.7(IL4R):​c.850-138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,010,894 control chromosomes in the GnomAD database, including 433,360 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 0.84 (55925 hom., cov: 32)
  • Exomes 𝑓: 0.94 (377435 hom.)
• Consequence: IL4R ENST00000395762.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.850-138A>G		intron_variant		ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.850-138A>G		intron_variant		1	NM_000418.4	ENSP00000379111	P1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128180 AN: 152076 Hom.: 55923 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 0.936 AC: 803418 AN: 858700 Hom.: 377435 AF XY: 0.939 AC XY: 420369 AN XY: 447592

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.887

Gnomad4 ASJ exome AF: 0.966

Gnomad4 EAS exome AF: 0.924

Gnomad4 SAS exome AF: 0.953

Gnomad4 FIN exome AF: 0.925

Gnomad4 NFE exome AF: 0.951

Gnomad4 OTH exome AF: 0.924

GnomAD4 genome AF: 0.842 AC: 128214 AN: 152194 Hom.: 55925 Cov.: 32 AF XY: 0.846 AC XY: 62949 AN XY: 74426

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.950

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.879

Alfa AF: 0.875 Hom.: 16282

Bravo AF: 0.829

Asia WGS AF: 0.894 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.7
DANN	Benign	0.67

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: rs3024668; hg19: chr16-27371949;