16-27364466-A-G

Variant names:

• chr16-27364466-A-G
• rs8832
• NM_000418.4:c.*636A>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.*636A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,200 control chromosomes in the GnomAD database, including 18,021 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 0.46 (17994 hom., cov: 32)
  • Exomes 𝑓: 0.49 (27 hom.)
• Consequence: IL4R NM_000418.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 55 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 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.*636A>G		3_prime_UTR	Exon 11 of 11	NP_000409.1
	IL4R	NM_001257406.2		c.*636A>G		3_prime_UTR	Exon 10 of 10	NP_001244335.1
	IL4R	NM_001257407.2		c.*636A>G		3_prime_UTR	Exon 11 of 11	NP_001244336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.*636A>G		3_prime_UTR	Exon 11 of 11	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.*636A>G		3_prime_UTR	Exon 10 of 10	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.*636A>G		3_prime_UTR	Exon 9 of 9	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70355 AN: 151866 Hom.: 18001 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.486 AC: 105 AN: 216 Hom.: 27 Cov.: 0 AF XY: 0.541 AC XY: 53 AN XY: 98

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.333 AC: 2 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 4 AN: 8

East Asian (EAS) AF: 0.500 AC: 8 AN: 16

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 79 AN: 158

Other (OTH) AF: 0.389 AC: 7 AN: 18

GnomAD4 genome AF: 0.463 AC: 70361 AN: 151984 Hom.: 17994 Cov.: 32 AF XY: 0.468 AC XY: 34757 AN XY: 74292

African (AFR) AF: 0.226 AC: 9352 AN: 41454

American (AMR) AF: 0.537 AC: 8202 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2465 AN: 5168

South Asian (SAS) AF: 0.559 AC: 2696 AN: 4826

European-Finnish (FIN) AF: 0.600 AC: 6328 AN: 10550

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37739 AN: 67940

Other (OTH) AF: 0.499 AC: 1053 AN: 2110

Alfa AF: 0.517 Hom.: 60252

Bravo AF: 0.447

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.37
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs8832; hg19: chr16-27375787;