rs2275913

Variant names:

• chr6-52186235-G-A
• rs2275913
• NM_002190.3:c.-197G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-52186235-G-A
• chr6-52186235-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.334
• Publications: 591 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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
IL17A	NM_002190.3	c.-197G>A		upstream_gene_variant		ENST00000648244.1	NP_002181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17A	ENST00000648244.1	c.-197G>A		upstream_gene_variant			NM_002190.3	ENSP00000497968.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43152 AN: 152006 Hom.: 7472 Cov.: 33

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

African (AFR) AF: 0.0957 AC: 3974 AN: 41528

American (AMR) AF: 0.242 AC: 3693 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2408 AN: 5174

South Asian (SAS) AF: 0.384 AC: 1856 AN: 4828

European-Finnish (FIN) AF: 0.472 AC: 4984 AN: 10558

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.357 AC: 24236 AN: 67978

Other (OTH) AF: 0.287 AC: 607 AN: 2112

Alfa AF: 0.324 Hom.: 18737

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

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
PhyloP100		-0.33
PromoterAI		0.016	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2275913; hg19: chr6-52051033;