rs8193037

Variant names:

• chr6-52186311-G-A
• rs8193037
• NM_002190.3:c.-121G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-52186311-G-A
• chr6-52186311-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002190.3(IL17A):​c.-121G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,042,394 control chromosomes in the GnomAD database, including 453 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 0.017 (60 hom., cov: 33)
  • Exomes 𝑓: 0.018 (393 hom.)
• Consequence: IL17A NM_002190.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 41 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002190.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17A	NM_002190.3	MANE Select	c.-121G>A		upstream_gene	N/A	NP_002181.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17A	ENST00000648244.1	MANE Select	c.-121G>A		upstream_gene	N/A	ENSP00000497968.1

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2616 AN: 152082 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00725

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0248

GnomAD4 exome AF: 0.0184 AC: 16337 AN: 890194 Hom.: 393 AF XY: 0.0176 AC XY: 8120 AN XY: 460724

African (AFR) AF: 0.00780 AC: 170 AN: 21808

American (AMR) AF: 0.0670 AC: 2469 AN: 36878

Ashkenazi Jewish (ASJ) AF: 0.00863 AC: 175 AN: 20280

East Asian (EAS) AF: 0.113 AC: 4035 AN: 35608

South Asian (SAS) AF: 0.00758 AC: 511 AN: 67382

European-Finnish (FIN) AF: 0.0131 AC: 662 AN: 50348

Middle Eastern (MID) AF: 0.0245 AC: 111 AN: 4526

European-Non Finnish (NFE) AF: 0.0121 AC: 7416 AN: 612564

Other (OTH) AF: 0.0193 AC: 788 AN: 40800

GnomAD4 genome AF: 0.0173 AC: 2627 AN: 152200 Hom.: 60 Cov.: 33 AF XY: 0.0188 AC XY: 1399 AN XY: 74428

African (AFR) AF: 0.00727 AC: 302 AN: 41524

American (AMR) AF: 0.0434 AC: 663 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.104 AC: 539 AN: 5170

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4828

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 830 AN: 67998

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0145 Hom.: 47

Bravo AF: 0.0205

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.4
DANN	Benign	0.91
PhyloP100		-0.19
PromoterAI		-0.016	Neutral

Splicing

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

Other links and lift over

dbSNP: rs8193037; hg19: chr6-52051109;