rs8193038

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002190.3(IL17A):​c.27+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 816,272 control chromosomes in the GnomAD database, including 432 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 0.024 ( 85 hom., cov: 32)
Exomes 𝑓: 0.020 ( 347 hom. )

Consequence

IL17A
NM_002190.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Publications

8 publications found
Variant links:
Genes affected
IL17A (HGNC:5981): (interleukin 17A) This gene is a member of the IL-17 receptor family which includes five members (IL-17RA-E) and the encoded protein is a proinflammatory cytokine produced by activated T cells. IL-17A-mediated downstream pathways induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins. The encoded protein elicits crucial impacts on host defense, cell trafficking, immune modulation, and tissue repair, with a key role in the induction of innate immune defenses. This cytokine stimulates non-hematopoietic cells and promotes chemokine production thereby attracting myeloid cells to inflammatory sites. This cytokine also regulates the activities of NF-kappaB and mitogen-activated protein kinases and can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). IL-17A plays a pivotal role in various infectious diseases, inflammatory and autoimmune disorders, and cancer. High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. The lung damage induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL17A. [provided by RefSeq, Sep 2020]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL17ANM_002190.3 linkc.27+126A>G intron_variant Intron 1 of 2 ENST00000648244.1 NP_002181.1 Q16552

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL17AENST00000648244.1 linkc.27+126A>G intron_variant Intron 1 of 2 NM_002190.3 ENSP00000497968.1 Q16552

Frequencies

GnomAD3 genomes
AF:
0.0235
AC:
3574
AN:
152208
Hom.:
81
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0275
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0463
Gnomad ASJ
AF:
0.00779
Gnomad EAS
AF:
0.108
Gnomad SAS
AF:
0.00869
Gnomad FIN
AF:
0.0173
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0124
Gnomad OTH
AF:
0.0301
GnomAD4 exome
AF:
0.0200
AC:
13261
AN:
663946
Hom.:
347
AF XY:
0.0191
AC XY:
6586
AN XY:
344102
show subpopulations
African (AFR)
AF:
0.0277
AC:
460
AN:
16622
American (AMR)
AF:
0.0631
AC:
1514
AN:
23996
Ashkenazi Jewish (ASJ)
AF:
0.00848
AC:
147
AN:
17326
East Asian (EAS)
AF:
0.118
AC:
3786
AN:
32066
South Asian (SAS)
AF:
0.00912
AC:
499
AN:
54700
European-Finnish (FIN)
AF:
0.0136
AC:
609
AN:
44618
Middle Eastern (MID)
AF:
0.0241
AC:
95
AN:
3936
European-Non Finnish (NFE)
AF:
0.0124
AC:
5428
AN:
437830
Other (OTH)
AF:
0.0220
AC:
723
AN:
32852
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
595
1191
1786
2382
2977
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
168
336
504
672
840
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0235
AC:
3585
AN:
152326
Hom.:
85
Cov.:
32
AF XY:
0.0254
AC XY:
1894
AN XY:
74492
show subpopulations
African (AFR)
AF:
0.0275
AC:
1142
AN:
41578
American (AMR)
AF:
0.0467
AC:
714
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00779
AC:
27
AN:
3468
East Asian (EAS)
AF:
0.109
AC:
563
AN:
5186
South Asian (SAS)
AF:
0.00849
AC:
41
AN:
4828
European-Finnish (FIN)
AF:
0.0173
AC:
184
AN:
10620
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.0125
AC:
847
AN:
68024
Other (OTH)
AF:
0.0298
AC:
63
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
185
370
556
741
926
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
44
88
132
176
220
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0142
Hom.:
6
Bravo
AF:
0.0279
Asia WGS
AF:
0.0620
AC:
215
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
5.8
DANN
Benign
0.63
PhyloP100
1.4
PromoterAI
0.015
Neutral
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs8193038; hg19: chr6-52051382; COSMIC: COSV60685304; API