Genetic Variant NM_000418.4:c.501C>T (chr16-27346606-C-T) – 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.501C>T(p.Asn167Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,613,662 control chromosomes in the GnomAD database, including 5,628 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 0.072 ( 481 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5147 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.721

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=-0.74).

BP7

Synonymous conserved (PhyloP=-0.721 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4 link	c.501C>T	p.Asn167Asn	synonymous_variant	Exon 6 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.501C>T	p.Asn167Asn	synonymous_variant	Exon 6 of 11	1	NM_000418.4	ENSP00000379111.2		P24394-1

Frequencies

GnomAD3 genomes

AF:

0.0722

AC:

10979

AN:

152128

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0573

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0491

Gnomad FIN

AF:

0.0794

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.0765

GnomAD3 exomes

AF:

0.0687

AC:

17271

AN:

251266

Hom.:

725

AF XY:

0.0698

AC XY:

9485

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.0379

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0518

Gnomad FIN exome

AF:

0.0766

Gnomad NFE exome

AF:

0.0893

Gnomad OTH exome

AF:

0.0840

GnomAD4 exome

AF:

0.0807

AC:

117967

AN:

1461416

Hom.:

5147

Cov.:

AF XY:

0.0803

AC XY:

58376

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.0549

Gnomad4 AMR exome

AF:

0.0413

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0525

Gnomad4 FIN exome

AF:

0.0750

Gnomad4 NFE exome

AF:

0.0875

Gnomad4 OTH exome

AF:

0.0786

GnomAD4 genome

AF:

0.0721

AC:

10980

AN:

152246

Hom.:

481

Cov.:

AF XY:

0.0703

AC XY:

5234

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0575

Gnomad4 AMR

AF:

0.0572

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0491

Gnomad4 FIN

AF:

0.0794

Gnomad4 NFE

AF:

0.0891

Gnomad4 OTH

AF:

0.0757

Alfa

AF:

0.0849

Hom.:

807

Bravo

AF:

0.0699

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0944

EpiControl

AF:

0.0933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.0

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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