dbSNP rs3024676: IL4R:c.900-15C>A (chr16-27362237-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000418.4(IL4R):c.900-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,609,810 control chromosomes in the GnomAD database, including 35,456 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 0.28 ( 9286 hom., cov: 32)

Exomes 𝑓: 0.17 ( 26170 hom. )

Consequence

IL4R
NM_000418.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.532

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.900-15C>A		intron_variant	Intron 10 of 10	ENST00000395762.7	NP_000409.1	P24394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 link	c.900-15C>A		intron_variant	Intron 10 of 10	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42991

AN:

151944

Hom.:

9246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.0995

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.178

AC:

44425

AN:

249658

Hom.:

5774

AF XY:

0.166

AC XY:

22440

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.0792

Gnomad SAS exome

AF:

0.0981

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.173

AC:

252519

AN:

1457748

Hom.:

26170

Cov.:

AF XY:

0.169

AC XY:

122566

AN XY:

724890

show subpopulations

Gnomad4 AFR exome

AF:

0.627

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.0713

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.283

AC:

43087

AN:

152062

Hom.:

9286

Cov.:

AF XY:

0.275

AC XY:

20456

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.607

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.0719

Gnomad4 SAS

AF:

0.0990

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.224

Hom.:

2673

Bravo

AF:

0.303

Asia WGS

AF:

0.155

AC:

538

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.3

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over