chr16-27364466-A-G

Position:

• chr16-27364466-A-G

Variant summary

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

The NM_000418.4(IL4R):​c.*636A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,200 control chromosomes in the GnomAD database, including 18,021 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 0.46 (17994 hom., cov: 32)
  • Exomes 𝑓: 0.49 (27 hom.)
• Consequence: IL4R NM_000418.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.*636A>G		3_prime_UTR_variant	11/11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.*636A>G		3_prime_UTR_variant	11/11	1	NM_000418.4	ENSP00000379111	P1
IL4R	ENST00000543915.6	c.*636A>G		3_prime_UTR_variant	10/10	1		ENSP00000441667	P1
IL4R	ENST00000170630.6	c.*636A>G		3_prime_UTR_variant	9/9	5		ENSP00000170630

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70355 AN: 151866 Hom.: 18001 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.486 AC: 105 AN: 216 Hom.: 27 Cov.: 0 AF XY: 0.541 AC XY: 53 AN XY: 98

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.463 AC: 70361 AN: 151984 Hom.: 17994 Cov.: 32 AF XY: 0.468 AC XY: 34757 AN XY: 74292

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.499

Alfa AF: 0.531 Hom.: 22985

Bravo AF: 0.447

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs8832; hg19: chr16-27375787;