rs3804513

Positions:

• chr6-52188399-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002190.3(IL17A):​c.230+594A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,270 control chromosomes in the GnomAD database, including 94 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 0.025 (94 hom., cov: 32)
• Consequence: IL17A NM_002190.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17A	NM_002190.3	c.230+594A>T		intron_variant		ENST00000648244.1	NP_002181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17A	ENST00000648244.1	c.230+594A>T		intron_variant			NM_002190.3	ENSP00000497968.1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3816 AN: 152152 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0252 AC: 3830 AN: 152270 Hom.: 94 Cov.: 32 AF XY: 0.0270 AC XY: 2013 AN XY: 74460

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0200 Hom.: 4

Bravo AF: 0.0297

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3804513; hg19: chr6-52053197;