6-52190537-C-T

Variant names:

• chr6-52190537-C-T
• rs1974226
• NM_002190.3:c.*1245C>T

Variant summary

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

The NM_002190.3(IL17A):​c.*1245C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,136 control chromosomes in the GnomAD database, including 1,863 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 0.15 (1863 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: IL17A NM_002190.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17A	NM_002190.3	c.*1245C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000648244.1	NP_002181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17A	ENST00000648244.1	c.*1245C>T		3_prime_UTR_variant	Exon 3 of 3		NM_002190.3	ENSP00000497968.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23290 AN: 152010 Hom.: 1862 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.153 AC: 23299 AN: 152128 Hom.: 1863 Cov.: 32 AF XY: 0.153 AC XY: 11414 AN XY: 74386

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0577

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.155

Alfa AF: 0.161 Hom.: 1624

Bravo AF: 0.146

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.64

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: rs1974226; hg19: chr6-52055335;