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16-27344950-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000418.4(IL4R):c.291T>C(p.Asp97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,614,058 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 50 hom. )

Consequence

IL4R
NM_000418.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.659
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-27344950-T-C is Benign according to our data. Variant chr16-27344950-T-C is described in ClinVar as [Benign]. Clinvar id is 778606.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.659 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2014/152266) while in subpopulation AFR AF= 0.0454 (1885/41552). AF 95% confidence interval is 0.0437. There are 52 homozygotes in gnomad4. There are 987 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL4RNM_000418.4 linkuse as main transcriptc.291T>C p.Asp97= synonymous_variant 5/11 ENST00000395762.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL4RENST00000395762.7 linkuse as main transcriptc.291T>C p.Asp97= synonymous_variant 5/111 NM_000418.4 P1P24394-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0132
AC:
2006
AN:
152148
Hom.:
50
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0453
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00609
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00358
AC:
901
AN:
251332
Hom.:
18
AF XY:
0.00275
AC XY:
373
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.0468
Gnomad AMR exome
AF:
0.00315
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000158
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00157
AC:
2289
AN:
1461792
Hom.:
50
Cov.:
40
AF XY:
0.00138
AC XY:
1000
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0510
Gnomad4 AMR exome
AF:
0.00333
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000124
Gnomad4 OTH exome
AF:
0.00429
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0132
AC:
2014
AN:
152266
Hom.:
52
Cov.:
32
AF XY:
0.0133
AC XY:
987
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0454
Gnomad4 AMR
AF:
0.00609
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00878
Hom.:
14
Bravo
AF:
0.0158
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
2.4
Dann
Benign
0.54

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.

Other links and lift over

dbSNP: rs112497527; hg19: chr16-27356271; API