NM_000418.4:c.209+781C>T

Variant names:

• chr16-27343040-C-T
• rs3024547
• NM_000418.4:c.209+781C>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.209+781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,144 control chromosomes in the GnomAD database, including 2,293 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 0.16 (2293 hom., cov: 32)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 14 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 (AFR) allele frequency at 95% confidence interval = 0.246 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.209+781C>T		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.209+781C>T		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.164+781C>T		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.209+781C>T		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.209+781C>T		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000912076.1		c.230+781C>T		intron	N/A	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24133 AN: 152026 Hom.: 2286 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.159 AC: 24182 AN: 152144 Hom.: 2293 Cov.: 32 AF XY: 0.155 AC XY: 11516 AN XY: 74376

African (AFR) AF: 0.250 AC: 10387 AN: 41472

American (AMR) AF: 0.107 AC: 1638 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0837 AC: 403 AN: 4814

European-Finnish (FIN) AF: 0.0967 AC: 1024 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9803 AN: 67994

Other (OTH) AF: 0.154 AC: 325 AN: 2112

Alfa AF: 0.159 Hom.: 453

Bravo AF: 0.164

Asia WGS AF: 0.0590 AC: 204 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	3.2
DANN	Benign	0.24
PhyloP100		-0.28
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: rs3024547; hg19: chr16-27354361;