6-52188798-T-C

Position:

• chr6-52188798-T-C

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.231-257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,950 control chromosomes in the GnomAD database, including 2,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2717 hom., cov: 32)
• Consequence: IL17A NM_002190.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0330

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=-0.83).
• BP6: Variant 6-52188798-T-C is Benign according to our data. Variant chr6-52188798-T-C is described in ClinVar as [Benign]. Clinvar id is 1178355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17A	NM_002190.3	c.231-257T>C		intron_variant		ENST00000648244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17A	ENST00000648244.1	c.231-257T>C		intron_variant			NM_002190.3	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24827 AN: 151830 Hom.: 2718 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.163 AC: 24812 AN: 151950 Hom.: 2717 Cov.: 32 AF XY: 0.160 AC XY: 11895 AN XY: 74264

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.205

Alfa AF: 0.186 Hom.: 380

Bravo AF: 0.155

Asia WGS AF: 0.0610 AC: 216 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.73

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: rs72916862; hg19: chr6-52053596;