chr16-27354975-T-C

Position:

• chr16-27354975-T-C

Variant summary

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

The NM_000418.4(IL4R):​c.671-833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 462,704 control chromosomes in the GnomAD database, including 1,587 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 0.088 (659 hom., cov: 32)
  • Exomes 𝑓: 0.073 (928 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.671-833T>C		intron_variant		ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.671-833T>C		intron_variant		1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13407 AN: 152106 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.0871

GnomAD3 exomes AF: 0.0696 AC: 10495 AN: 150796 Hom.: 448 AF XY: 0.0691 AC XY: 5527 AN XY: 79980

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.000277

Gnomad SAS exome AF: 0.0524

Gnomad FIN exome AF: 0.0734

Gnomad NFE exome AF: 0.0851

Gnomad OTH exome AF: 0.0852

GnomAD4 exome AF: 0.0728 AC: 22610 AN: 310480 Hom.: 928 Cov.: 0 AF XY: 0.0705 AC XY: 12280 AN XY: 174082

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.000338

Gnomad4 SAS exome AF: 0.0523

Gnomad4 FIN exome AF: 0.0724

Gnomad4 NFE exome AF: 0.0827

Gnomad4 OTH exome AF: 0.0836

GnomAD4 genome AF: 0.0881 AC: 13415 AN: 152224 Hom.: 659 Cov.: 32 AF XY: 0.0862 AC XY: 6419 AN XY: 74444

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.0849

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0914 Hom.: 164

Bravo AF: 0.0891

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.55

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: rs3024632; hg19: chr16-27366296;