6-52187159-G-T

Position:

• chr6-52187159-G-T

Variant summary

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

The NM_002190.3(IL17A):​c.28-444G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,146 control chromosomes in the GnomAD database, including 2,720 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 0.16 (2720 hom., cov: 32)
• Consequence: IL17A NM_002190.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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 (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17A	NM_002190.3	c.28-444G>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.28-444G>T		intron_variant			NM_002190.3	ENSP00000497968	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24688 AN: 152028 Hom.: 2722 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.162 AC: 24671 AN: 152146 Hom.: 2720 Cov.: 32 AF XY: 0.159 AC XY: 11832 AN XY: 74378

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.204

Alfa AF: 0.215 Hom.: 5299

Bravo AF: 0.154

Asia WGS AF: 0.0610 AC: 214 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	3.1
DANN	Benign	0.67

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: rs10484879; hg19: chr6-52051957;