rs8193038

Variant names:

• chr6-52186584-A-G
• rs8193038
• NM_002190.3:c.27+126A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 8 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=-0.62).
• 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
IL17A	NM_002190.3	c.27+126A>G		intron_variant	Intron 1 of 2	ENST00000648244.1	NP_002181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17A	ENST00000648244.1	c.27+126A>G		intron_variant	Intron 1 of 2		NM_002190.3	ENSP00000497968.1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3574 AN: 152208 Hom.: 81 Cov.: 32

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

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

GnomAD4 genome AF: 0.0235 AC: 3585 AN: 152326 Hom.: 85 Cov.: 32 AF XY: 0.0254 AC XY: 1894 AN XY: 74492

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

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

Other links and lift over

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