Variant 16-27344896-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000418.4(IL4R):c.237C>T(p.Asn79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,614,150 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 17 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.72

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-27344896-C-T is Benign according to our data. Variant chr16-27344896-C-T is described in ClinVar as [Benign]. Clinvar id is 718605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0065 (990/152318) while in subpopulation AFR AF= 0.0227 (944/41570). AF 95% confidence interval is 0.0215. There are 18 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4R	NM_000418.4 linkuse as main transcript	c.237C>T	p.Asn79=	synonymous_variant	5/11	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7 linkuse as main transcript	c.237C>T	p.Asn79=	synonymous_variant	5/11	1	NM_000418.4	ENSP00000379111	P1	P24394-1

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00193

AC:

485

AN:

251198

Hom.:

AF XY:

0.00152

AC XY:

206

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.0247

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000983

AC:

1437

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000853

AC XY:

620

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000303

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.00650

AC:

990

AN:

152318

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

492

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00813

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

DANN

Benign

0.77

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over