16-27360628-A-G

Variant names:

• chr16-27360628-A-G
• rs3024668
• NM_000418.4:c.850-138A>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.850-138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,010,894 control chromosomes in the GnomAD database, including 433,360 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 0.84 (55925 hom., cov: 32)
  • Exomes 𝑓: 0.94 (377435 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 14 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 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.850-138A>G		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.850-138A>G		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.805-138A>G		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.850-138A>G		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.850-138A>G		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.805-138A>G		intron	N/A	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128180 AN: 152076 Hom.: 55923 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 0.936 AC: 803418 AN: 858700 Hom.: 377435 AF XY: 0.939 AC XY: 420369 AN XY: 447592

African (AFR) AF: 0.590 AC: 12466 AN: 21138

American (AMR) AF: 0.887 AC: 34668 AN: 39074

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 19897 AN: 20606

East Asian (EAS) AF: 0.924 AC: 33938 AN: 36728

South Asian (SAS) AF: 0.953 AC: 67245 AN: 70576

European-Finnish (FIN) AF: 0.925 AC: 44585 AN: 48188

Middle Eastern (MID) AF: 0.961 AC: 2748 AN: 2860

European-Non Finnish (NFE) AF: 0.951 AC: 550960 AN: 579578

Other (OTH) AF: 0.924 AC: 36911 AN: 39952

GnomAD4 genome AF: 0.842 AC: 128214 AN: 152194 Hom.: 55925 Cov.: 32 AF XY: 0.846 AC XY: 62949 AN XY: 74426

African (AFR) AF: 0.591 AC: 24488 AN: 41468

American (AMR) AF: 0.884 AC: 13516 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3342 AN: 3472

East Asian (EAS) AF: 0.925 AC: 4787 AN: 5176

South Asian (SAS) AF: 0.950 AC: 4587 AN: 4830

European-Finnish (FIN) AF: 0.927 AC: 9837 AN: 10608

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64615 AN: 68026

Other (OTH) AF: 0.879 AC: 1857 AN: 2112

Alfa AF: 0.869 Hom.: 16414

Bravo AF: 0.829

Asia WGS AF: 0.894 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.7
DANN	Benign	0.67
PhyloP100		0.12
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: rs3024668; hg19: chr16-27371949;