rs7747909

chr6-52189451-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002190.3(IL17A):c.*159G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 570,854 control chromosomes in the GnomAD database, including 12,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2918 hom., cov: 32)
  • Exomes 𝑓: 0.20 (9457 hom.)
• Consequence: IL17A NM_002190.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-52189451-G-A is Benign according to our data. Variant chr6-52189451-G-A is described in ClinVar as [Benign]. Clinvar id is 1266947.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17A	NM_002190.3	c.*159G>A		3_prime_UTR_variant	3/3	ENST00000648244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17A	ENST00000648244.1	c.*159G>A		3_prime_UTR_variant	3/3		NM_002190.3	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27345 AN: 152024 Hom.: 2920 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.200 AC: 83689 AN: 418712 Hom.: 9457 Cov.: 4 AF XY: 0.199 AC XY: 43391 AN XY: 217974

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.000370

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.180 AC: 27331 AN: 152142 Hom.: 2918 Cov.: 32 AF XY: 0.177 AC XY: 13142 AN XY: 74382

Gnomad4 AFR AF: 0.0978

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.217

Alfa AF: 0.224 Hom.: 3866

Bravo AF: 0.173

Asia WGS AF: 0.0630 AC: 223 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

This variant is associated with the following publications: (PMID: 26765636) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.4
Dann	Benign	0.55

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: rs7747909; hg19: chr6-52054249;