16-27335033-T-C

Variant names:

• chr16-27335033-T-C
• rs2283563
• NM_000418.4:c.-19+4835T>C

Variant summary

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

The NM_000418.4(IL4R):​c.-19+4835T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,956 control chromosomes in the GnomAD database, including 34,916 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 0.67 (34916 hom., cov: 32)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• Publications: 25 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	NM_000418.4	MANE Select	c.-19+4835T>C		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.-18-5153T>C		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.-307-5153T>C		intron	N/A	NP_001244336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.-19+4835T>C		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.-18-5153T>C		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000563002.5	TSL:5	c.-18-5153T>C		intron	N/A	ENSP00000456930.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102228 AN: 151836 Hom.: 34867 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.673 AC: 102342 AN: 151956 Hom.: 34916 Cov.: 32 AF XY: 0.663 AC XY: 49225 AN XY: 74244

African (AFR) AF: 0.735 AC: 30482 AN: 41466

American (AMR) AF: 0.605 AC: 9235 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2449 AN: 3472

East Asian (EAS) AF: 0.512 AC: 2653 AN: 5178

South Asian (SAS) AF: 0.544 AC: 2620 AN: 4818

European-Finnish (FIN) AF: 0.540 AC: 5701 AN: 10560

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.690 AC: 46872 AN: 67914

Other (OTH) AF: 0.697 AC: 1469 AN: 2108

Alfa AF: 0.682 Hom.: 55837

Bravo AF: 0.682

Asia WGS AF: 0.528 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.26
PhyloP100		-3.4
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: rs2283563; hg19: chr16-27346354;