rs3024632

Variant names:

• chr16-27354975-T-C
• rs3024632
• NM_000418.4:c.671-833T>C

Variant summary

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

The NM_000418.4(IL4R):​c.671-833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 462,704 control chromosomes in the GnomAD database, including 1,587 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 0.088 (659 hom., cov: 32)
  • Exomes 𝑓: 0.073 (928 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 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.671-833T>C		intron	N/A	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.671-833T>C		intron	N/A	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.626-833T>C		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.671-833T>C		intron	N/A	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.671-833T>C		intron	N/A	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.692-833T>C		intron	N/A	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13407 AN: 152106 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.0871

GnomAD2 exomes AF: 0.0696 AC: 10495 AN: 150796 AF XY: 0.0691

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.000277

Gnomad FIN exome AF: 0.0734

Gnomad NFE exome AF: 0.0851

Gnomad OTH exome AF: 0.0852

GnomAD4 exome AF: 0.0728 AC: 22610 AN: 310480 Hom.: 928 Cov.: 0 AF XY: 0.0705 AC XY: 12280 AN XY: 174082

African (AFR) AF: 0.133 AC: 1125 AN: 8488

American (AMR) AF: 0.0414 AC: 1114 AN: 26920

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 1204 AN: 10634

East Asian (EAS) AF: 0.000338 AC: 3 AN: 8874

South Asian (SAS) AF: 0.0523 AC: 3096 AN: 59238

European-Finnish (FIN) AF: 0.0724 AC: 2033 AN: 28088

Middle Eastern (MID) AF: 0.120 AC: 330 AN: 2752

European-Non Finnish (NFE) AF: 0.0827 AC: 12542 AN: 151574

Other (OTH) AF: 0.0836 AC: 1163 AN: 13912

GnomAD4 genome AF: 0.0881 AC: 13415 AN: 152224 Hom.: 659 Cov.: 32 AF XY: 0.0862 AC XY: 6419 AN XY: 74444

African (AFR) AF: 0.122 AC: 5046 AN: 41522

American (AMR) AF: 0.0642 AC: 983 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0505 AC: 244 AN: 4830

European-Finnish (FIN) AF: 0.0746 AC: 791 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5771 AN: 67992

Other (OTH) AF: 0.0866 AC: 183 AN: 2112

Alfa AF: 0.0920 Hom.: 168

Bravo AF: 0.0891

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.54
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: rs3024632; hg19: chr16-27366296;