chr16-27364221-G-A

Variant names:

• chr16-27364221-G-A
• rs1049631
• NM_000418.4:c.*391G>A

Variant summary

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

The NM_000418.4(IL4R):​c.*391G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 180,092 control chromosomes in the GnomAD database, including 20,850 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 0.45 (17034 hom., cov: 33)
  • Exomes 𝑓: 0.51 (3816 hom.)
• Consequence: IL4R NM_000418.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 21 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 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.*391G>A		3_prime_UTR	Exon 11 of 11	NP_000409.1
	IL4R	NM_001257406.2		c.*391G>A		3_prime_UTR	Exon 10 of 10	NP_001244335.1
	IL4R	NM_001257407.2		c.*391G>A		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.*391G>A		3_prime_UTR	Exon 11 of 11	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.*391G>A		3_prime_UTR	Exon 10 of 10	ENSP00000441667.2
	IL4R	ENST00000565352.1	TSL:5	c.348G>A	p.Thr116Thr	synonymous	Exon 5 of 5	ENSP00000461268.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68590 AN: 151932 Hom.: 17041 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.493

GnomAD2 exomes AF: 0.507 AC: 2259 AN: 4452 AF XY: 0.515

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.688

Gnomad EAS exome AF: 0.413

Gnomad FIN exome AF: 0.667

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.510 AC: 14316 AN: 28044 Hom.: 3816 Cov.: 0 AF XY: 0.514 AC XY: 7249 AN XY: 14098

African (AFR) AF: 0.217 AC: 215 AN: 992

American (AMR) AF: 0.519 AC: 967 AN: 1864

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 533 AN: 938

East Asian (EAS) AF: 0.356 AC: 530 AN: 1488

South Asian (SAS) AF: 0.499 AC: 525 AN: 1052

European-Finnish (FIN) AF: 0.556 AC: 676 AN: 1216

Middle Eastern (MID) AF: 0.493 AC: 66 AN: 134

European-Non Finnish (NFE) AF: 0.533 AC: 9939 AN: 18656

Other (OTH) AF: 0.508 AC: 865 AN: 1704

GnomAD4 genome AF: 0.451 AC: 68598 AN: 152048 Hom.: 17034 Cov.: 33 AF XY: 0.456 AC XY: 33926 AN XY: 74324

African (AFR) AF: 0.220 AC: 9138 AN: 41482

American (AMR) AF: 0.525 AC: 8011 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1998 AN: 3464

East Asian (EAS) AF: 0.440 AC: 2275 AN: 5168

South Asian (SAS) AF: 0.548 AC: 2645 AN: 4828

European-Finnish (FIN) AF: 0.580 AC: 6136 AN: 10584

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.543 AC: 36884 AN: 67964

Other (OTH) AF: 0.490 AC: 1029 AN: 2102

Alfa AF: 0.512 Hom.: 38377

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.44
PhyloP100		-0.34
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: rs1049631; hg19: chr16-27375542;