rs3024560

Variant names:

• chr16-27345346-T-G
• rs3024560
• NM_000418.4:c.361+326T>G

Variant summary

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

The NM_000418.4(IL4R):​c.361+326T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 438,880 control chromosomes in the GnomAD database, including 31,402 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 0.38 (10975 hom., cov: 31)
  • Exomes 𝑓: 0.37 (20427 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 22 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 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.361+326T>G		intron	N/A	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.361+326T>G		intron	N/A	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.316+326T>G		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.361+326T>G		intron	N/A	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.361+326T>G		intron	N/A	ENSP00000441667.2	P24394-1
	IL4R	ENST00000562968.1	TSL:3	c.*127T>G		3_prime_UTR	Exon 2 of 2	ENSP00000456669.1	H3BSE7

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57019 AN: 151826 Hom.: 10957 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.374 AC: 107314 AN: 286936 Hom.: 20427 Cov.: 0 AF XY: 0.377 AC XY: 58768 AN XY: 155780

African (AFR) AF: 0.425 AC: 3694 AN: 8688

American (AMR) AF: 0.407 AC: 8099 AN: 19902

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 2429 AN: 8324

East Asian (EAS) AF: 0.543 AC: 7039 AN: 12952

South Asian (SAS) AF: 0.389 AC: 19421 AN: 49952

European-Finnish (FIN) AF: 0.300 AC: 4083 AN: 13604

Middle Eastern (MID) AF: 0.315 AC: 863 AN: 2740

European-Non Finnish (NFE) AF: 0.361 AC: 56264 AN: 155874

Other (OTH) AF: 0.364 AC: 5422 AN: 14900

GnomAD4 genome AF: 0.376 AC: 57095 AN: 151944 Hom.: 10975 Cov.: 31 AF XY: 0.373 AC XY: 27737 AN XY: 74298

African (AFR) AF: 0.419 AC: 17383 AN: 41444

American (AMR) AF: 0.371 AC: 5666 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2690 AN: 5162

South Asian (SAS) AF: 0.390 AC: 1877 AN: 4816

European-Finnish (FIN) AF: 0.282 AC: 2975 AN: 10560

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24112 AN: 67914

Other (OTH) AF: 0.379 AC: 800 AN: 2112

Alfa AF: 0.362 Hom.: 17358

Bravo AF: 0.385

Asia WGS AF: 0.438 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.47
PhyloP100		-1.6
PromoterAI		-0.069	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: rs3024560; hg19: chr16-27356667; COSMIC: COSV50166073; COSMIC: COSV50166073;