rs1049631

Positions:

• chr16-27364221-G-A
• chr16-27364221-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-27364221-G-A is Benign according to our data. Variant chr16-27364221-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4	c.*391G>A		3_prime_UTR_variant	11/11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.*391G>A		3_prime_UTR_variant	11/11	1	NM_000418.4	ENSP00000379111.2
IL4R	ENST00000543915.6	c.*391G>A		3_prime_UTR_variant	10/10	1		ENSP00000441667.2
IL4R	ENST00000565352.1	c.348G>A	p.Thr116Thr	synonymous_variant	5/5	5		ENSP00000461268.1
IL4R	ENST00000170630.6	c.*391G>A		3_prime_UTR_variant	9/9	5		ENSP00000170630.3

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

GnomAD3 exomes AF: 0.507 AC: 2259 AN: 4452 Hom.: 608 AF XY: 0.515 AC XY: 1128 AN XY: 2190

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 SAS exome AF: 0.507

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

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.508

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

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.490

Alfa AF: 0.522 Hom.: 28395

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs1049631; hg19: chr16-27375542;