rs3024543

Variant names:

• chr16-27341909-G-A
• rs3024543
• NM_000418.4:c.71-212G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-27341909-G-A
• chr16-27341909-G-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.71-212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 547,260 control chromosomes in the GnomAD database, including 5,103 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 0.14 (1645 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3458 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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.71-212G>A		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.71-212G>A		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.26-212G>A		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.71-212G>A		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.71-212G>A		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.26-212G>A		intron	N/A	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21092 AN: 152084 Hom.: 1642 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.124 AC: 48949 AN: 395058 Hom.: 3458 AF XY: 0.123 AC XY: 25316 AN XY: 205678

African (AFR) AF: 0.182 AC: 2035 AN: 11186

American (AMR) AF: 0.0825 AC: 1229 AN: 14890

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 1976 AN: 12472

East Asian (EAS) AF: 0.000321 AC: 9 AN: 28020

South Asian (SAS) AF: 0.0904 AC: 3046 AN: 33690

European-Finnish (FIN) AF: 0.0949 AC: 2635 AN: 27758

Middle Eastern (MID) AF: 0.183 AC: 328 AN: 1796

European-Non Finnish (NFE) AF: 0.143 AC: 34566 AN: 241778

Other (OTH) AF: 0.133 AC: 3125 AN: 23468

GnomAD4 genome AF: 0.139 AC: 21123 AN: 152202 Hom.: 1645 Cov.: 32 AF XY: 0.135 AC XY: 10065 AN XY: 74418

African (AFR) AF: 0.179 AC: 7444 AN: 41532

American (AMR) AF: 0.0988 AC: 1511 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.0851 AC: 410 AN: 4820

European-Finnish (FIN) AF: 0.0970 AC: 1028 AN: 10598

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

European-Non Finnish (NFE) AF: 0.145 AC: 9831 AN: 67998

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.131 Hom.: 629

Bravo AF: 0.141

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-0.24
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: rs3024543; hg19: chr16-27353230;