rs2275913

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002190.3(IL17A):​c.-197G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,124 control chromosomes in the GnomAD database, including 7,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 7469 hom., cov: 33)

Consequence

IL17A
NM_002190.3 upstream_gene

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.334
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 6-52186235-G-A is Benign according to our data. Variant chr6-52186235-G-A is described in ClinVar as [Benign]. Clinvar id is 1278437.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL17ANM_002190.3 linkc.-197G>A upstream_gene_variant ENST00000648244.1 NP_002181.1 Q16552

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL17AENST00000648244.1 linkc.-197G>A upstream_gene_variant NM_002190.3 ENSP00000497968.1 Q16552

Frequencies

GnomAD3 genomes
AF:
0.284
AC:
43152
AN:
152006
Hom.:
7472
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0959
Gnomad AMI
AF:
0.320
Gnomad AMR
AF:
0.242
Gnomad ASJ
AF:
0.293
Gnomad EAS
AF:
0.466
Gnomad SAS
AF:
0.383
Gnomad FIN
AF:
0.472
Gnomad MID
AF:
0.277
Gnomad NFE
AF:
0.357
Gnomad OTH
AF:
0.288
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.284
AC:
43144
AN:
152124
Hom.:
7469
Cov.:
33
AF XY:
0.291
AC XY:
21659
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0957
Gnomad4 AMR
AF:
0.242
Gnomad4 ASJ
AF:
0.293
Gnomad4 EAS
AF:
0.465
Gnomad4 SAS
AF:
0.384
Gnomad4 FIN
AF:
0.472
Gnomad4 NFE
AF:
0.357
Gnomad4 OTH
AF:
0.287
Alfa
AF:
0.334
Hom.:
6199
Bravo
AF:
0.255
Asia WGS
AF:
0.372
AC:
1293
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Nov 12, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22537748, 21672939, 22028838, 29372577, 25595174, 29985710, 23778030) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
4.8
DANN
Benign
0.75

Splicing

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: rs2275913; hg19: chr6-52051033; API