rs1801275

chr16-27363079-A-Gchr16-27363079-A-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.1727A>G(p.Gln576Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,613,910 control chromosomes in the GnomAD database, including 54,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (12743 hom., cov: 33)
  • Exomes 𝑓: 0.22 (41529 hom.)
• Consequence: IL4R NM_000418.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.05

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 (MetaRNN=1.1686489E-6).
• BP6: Variant 16-27363079-A-G is Benign according to our data. Variant chr16-27363079-A-G is described in ClinVar as [Benign]. Clinvar id is 14665.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4R	NM_000418.4	c.1727A>G	p.Gln576Arg	missense_variant	11/11	ENST00000395762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4R	ENST00000395762.7	c.1727A>G	p.Gln576Arg	missense_variant	11/11	1	NM_000418.4	P1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52747 AN: 152070 Hom.: 12686 Cov.: 33

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.306

GnomAD3 exomes AF: 0.248 AC: 61954 AN: 250126 Hom.: 9564 AF XY: 0.235 AC XY: 31920 AN XY: 135542

Gnomad AFR exome AF: 0.703

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.222

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.225 AC: 328389 AN: 1461722 Hom.: 41529 Cov.: 36 AF XY: 0.222 AC XY: 161640 AN XY: 727180

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.347 AC: 52863 AN: 152188 Hom.: 12743 Cov.: 33 AF XY: 0.343 AC XY: 25484 AN XY: 74404

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.305

Alfa AF: 0.226 Hom.: 10956

Bravo AF: 0.369

TwinsUK AF: 0.211 AC: 781

ALSPAC AF: 0.215 AC: 829

ESP6500AA AF: 0.674 AC: 2963

ESP6500EA AF: 0.204 AC: 1753

ExAC AF: 0.254 AC: 30865

Asia WGS AF: 0.278 AC: 967 AN: 3478

EpiCase AF: 0.195

EpiControl AF: 0.189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Atopy, resistance to Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Feb 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	13
Dann	Benign	0.24
DEOGEN2	Benign	0.074	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.025	N
MetaRNN	Benign	0.0000012	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.5	N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.89	N;N;.
REVEL	Benign	0.065
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.031
MPC		0.14
ClinPred		0.00026	T
GERP RS		2.8
Varity_R		0.018
gMVP		0.14

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: rs1801275; hg19: chr16-27374400; COSMIC: COSV50142227; COSMIC: COSV50142227;