rs3024614

Variant names:

• chr16-27353024-G-A
• rs3024614
• NM_000418.4:c.670+328G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-27353024-G-A
• chr16-27353024-G-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.670+328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,204 control chromosomes in the GnomAD database, including 56,376 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 0.85 (56376 hom., cov: 33)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.94 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.670+328G>A		intron	N/A	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.670+328G>A		intron	N/A	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.625+328G>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.670+328G>A		intron	N/A	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.670+328G>A		intron	N/A	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.691+328G>A		intron	N/A	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128966 AN: 152086 Hom.: 56359 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.848 AC: 129016 AN: 152204 Hom.: 56376 Cov.: 33 AF XY: 0.851 AC XY: 63306 AN XY: 74420

African (AFR) AF: 0.610 AC: 25303 AN: 41468

American (AMR) AF: 0.913 AC: 13963 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3328 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4739 AN: 5190

South Asian (SAS) AF: 0.940 AC: 4537 AN: 4828

European-Finnish (FIN) AF: 0.920 AC: 9763 AN: 10612

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64344 AN: 68026

Other (OTH) AF: 0.879 AC: 1859 AN: 2114

Alfa AF: 0.914 Hom.: 94872

Bravo AF: 0.838

Asia WGS AF: 0.892 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.017
DANN	Benign	0.52
PhyloP100		-1.3
PromoterAI		-0.014	Neutral
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: rs3024614; hg19: chr16-27364345;