rs6498012

Positions:

• chr16-27320653-C-G
• chr16-27320653-C-T

Variant summary

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

The ENST00000395762.7(IL4R):​c.-152+6633C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,136 control chromosomes in the GnomAD database, including 30,452 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 0.63 (30452 hom., cov: 33)
• Consequence: IL4R ENST00000395762.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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 (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.-152+6633C>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.-152+6633C>G		intron_variant		1	NM_000418.4	ENSP00000379111	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95585 AN: 152018 Hom.: 30418 Cov.: 33

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.623

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.629 AC: 95664 AN: 152136 Hom.: 30452 Cov.: 33 AF XY: 0.628 AC XY: 46726 AN XY: 74378

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.618

Alfa AF: 0.635 Hom.: 3821

Bravo AF: 0.627

Asia WGS AF: 0.471 AC: 1637 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	2.6
DANN	Benign	0.39

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: rs6498012; hg19: chr16-27331974;