Genetic Variant NM_000418.4:c.2397T>C (chr16-27363749-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000418.4(IL4R):c.2397T>C(p.Pro799Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00787 in 1,613,188 control chromosomes in the GnomAD database, including 644 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 0.038 ( 339 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 305 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-1.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.2397T>C	p.Pro799Pro	synonymous_variant	Exon 11 of 11	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.2397T>C	p.Pro799Pro	synonymous_variant	Exon 11 of 11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5823

AN:

152142

Hom.:

335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0110

AC:

2754

AN:

250288

Hom.:

136

AF XY:

0.00845

AC XY:

1145

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.00995

Gnomad ASJ exome

AF:

0.00747

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.0000477

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.00470

AC:

6862

AN:

1460928

Hom.:

305

Cov.:

AF XY:

0.00412

AC XY:

2993

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00685

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000994

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.0383

AC:

5838

AN:

152260

Hom.:

339

Cov.:

AF XY:

0.0370

AC XY:

2757

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0258

Hom.:

101

Bravo

AF:

0.0447

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.69

DANN

Benign

0.40

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