rs3024656

Variant names:

• chr16-27358288-G-A
• rs3024656
• NM_000418.4:c.771-628G>A

Variant summary

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

The NM_000418.4(IL4R):​c.771-628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,186 control chromosomes in the GnomAD database, including 4,069 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 0.20 (4069 hom., cov: 33)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.771-628G>A		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.771-628G>A		intron_variant	Intron 8 of 10	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30408 AN: 152068 Hom.: 4071 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.200 AC: 30396 AN: 152186 Hom.: 4069 Cov.: 33 AF XY: 0.192 AC XY: 14304 AN XY: 74398

African (AFR) AF: 0.0548 AC: 2276 AN: 41536

American (AMR) AF: 0.190 AC: 2907 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5192

South Asian (SAS) AF: 0.173 AC: 833 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1950 AN: 10568

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20361 AN: 67982

Other (OTH) AF: 0.244 AC: 516 AN: 2114

Alfa AF: 0.259 Hom.: 1702

Bravo AF: 0.195

Asia WGS AF: 0.0790 AC: 277 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	4.2
DANN	Benign	0.46
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3024656; hg19: chr16-27369609;