16-27348523-G-A

Variant names:

• chr16-27348523-G-A
• rs3024585
• NM_000418.4:c.513+1905G>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.513+1905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,140 control chromosomes in the GnomAD database, including 17,360 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 0.47 (17360 hom., cov: 34)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 27 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 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.513+1905G>A		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.513+1905G>A		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.468+1905G>A		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.513+1905G>A		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.513+1905G>A		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.468+1905G>A		intron	N/A	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71979 AN: 152022 Hom.: 17337 Cov.: 34

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.474 AC: 72048 AN: 152140 Hom.: 17360 Cov.: 34 AF XY: 0.473 AC XY: 35186 AN XY: 74388

African (AFR) AF: 0.479 AC: 19881 AN: 41502

American (AMR) AF: 0.533 AC: 8149 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3472

East Asian (EAS) AF: 0.639 AC: 3310 AN: 5180

South Asian (SAS) AF: 0.536 AC: 2584 AN: 4822

European-Finnish (FIN) AF: 0.388 AC: 4101 AN: 10576

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30871 AN: 67986

Other (OTH) AF: 0.478 AC: 1012 AN: 2116

Alfa AF: 0.468 Hom.: 51969

Bravo AF: 0.486

Asia WGS AF: 0.593 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.78
PhyloP100		-1.1
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: rs3024585; hg19: chr16-27359844;