rs3024537

Variant names:

• chr16-27341498-G-A
• rs3024537
• NM_000418.4:c.71-623G>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.71-623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,126 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.12 (1238 hom., cov: 32)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 12 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	NM_000418.4	MANE Select	c.71-623G>A		intron	N/A	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.71-623G>A		intron	N/A	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.25+185G>A		intron	N/A	NP_001244336.1	P24394-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.71-623G>A		intron	N/A	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.71-623G>A		intron	N/A	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.71-602G>A		intron	N/A	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18358 AN: 152008 Hom.: 1236 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.121 AC: 18380 AN: 152126 Hom.: 1238 Cov.: 32 AF XY: 0.118 AC XY: 8739 AN XY: 74368

African (AFR) AF: 0.118 AC: 4886 AN: 41480

American (AMR) AF: 0.0919 AC: 1404 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4830

European-Finnish (FIN) AF: 0.0964 AC: 1020 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9791 AN: 67988

Other (OTH) AF: 0.130 AC: 273 AN: 2106

Alfa AF: 0.138 Hom.: 1894

Bravo AF: 0.120

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.39
PhyloP100		-1.1
PromoterAI		-0.0016	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3024537;

hg19: chr16-27352819;