rs4787423

Variant names:

• chr16-27356013-C-T
• rs4787423
• NM_000418.4:c.770+106C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000418.4(IL4R):​c.770+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 705,110 control chromosomes in the GnomAD database, including 258,556 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 0.81 (50607 hom., cov: 29)
  • Exomes 𝑓: 0.87 (207949 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 23 publications found

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]

IL4R Gene-Disease associations (from GenCC):

• IgE responsiveness, atopic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.770+106C>T		intron_variant	Intron 8 of 10	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.770+106C>T		intron_variant	Intron 8 of 10	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 122897 AN: 151616 Hom.: 50569 Cov.: 29

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.866 AC: 479169 AN: 553376 Hom.: 207949 AF XY: 0.868 AC XY: 258215 AN XY: 297324

African (AFR) AF: 0.662 AC: 10237 AN: 15468

American (AMR) AF: 0.915 AC: 29857 AN: 32642

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 14286 AN: 16628

East Asian (EAS) AF: 0.920 AC: 31341 AN: 34084

South Asian (SAS) AF: 0.891 AC: 51884 AN: 58262

European-Finnish (FIN) AF: 0.848 AC: 31518 AN: 37184

Middle Eastern (MID) AF: 0.855 AC: 3237 AN: 3784

European-Non Finnish (NFE) AF: 0.864 AC: 281147 AN: 325256

Other (OTH) AF: 0.853 AC: 25662 AN: 30068

GnomAD4 genome AF: 0.811 AC: 122988 AN: 151734 Hom.: 50607 Cov.: 29 AF XY: 0.813 AC XY: 60268 AN XY: 74102

African (AFR) AF: 0.659 AC: 27189 AN: 41228

American (AMR) AF: 0.874 AC: 13353 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3003 AN: 3470

East Asian (EAS) AF: 0.913 AC: 4700 AN: 5148

South Asian (SAS) AF: 0.890 AC: 4292 AN: 4822

European-Finnish (FIN) AF: 0.845 AC: 8853 AN: 10480

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58673 AN: 67984

Other (OTH) AF: 0.840 AC: 1773 AN: 2110

Alfa AF: 0.846 Hom.: 202566

Bravo AF: 0.807

Asia WGS AF: 0.877 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4787423; hg19: chr16-27367334;