16-27342036-C-T

Variant names:

• chr16-27342036-C-T
• rs3024544
• NM_000418.4:c.71-85C>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.71-85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,486,994 control chromosomes in the GnomAD database, including 13,785 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 0.12 (1237 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12548 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 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.71-85C>T		intron	N/A	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.71-85C>T		intron	N/A	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.26-85C>T		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.71-85C>T		intron	N/A	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.71-85C>T		intron	N/A	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.71-64C>T		intron	N/A	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18307 AN: 152122 Hom.: 1235 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.132 AC: 176253 AN: 1334754 Hom.: 12548 Cov.: 19 AF XY: 0.132 AC XY: 87214 AN XY: 662694

African (AFR) AF: 0.118 AC: 3659 AN: 31090

American (AMR) AF: 0.0672 AC: 2760 AN: 41054

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3550 AN: 22654

East Asian (EAS) AF: 0.000516 AC: 20 AN: 38734

South Asian (SAS) AF: 0.0924 AC: 7105 AN: 76928

European-Finnish (FIN) AF: 0.0967 AC: 4039 AN: 41766

Middle Eastern (MID) AF: 0.170 AC: 860 AN: 5058

European-Non Finnish (NFE) AF: 0.144 AC: 147078 AN: 1021556

Other (OTH) AF: 0.128 AC: 7182 AN: 55914

GnomAD4 genome AF: 0.120 AC: 18328 AN: 152240 Hom.: 1237 Cov.: 32 AF XY: 0.117 AC XY: 8708 AN XY: 74428

African (AFR) AF: 0.116 AC: 4829 AN: 41546

American (AMR) AF: 0.0915 AC: 1399 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 519 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4830

European-Finnish (FIN) AF: 0.0967 AC: 1026 AN: 10610

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9796 AN: 67986

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.132 Hom.: 1507

Bravo AF: 0.120

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.51
PhyloP100		-0.75
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: rs3024544; hg19: chr16-27353357;