rs7747909

Variant names:

• chr6-52189451-G-A
• rs7747909
• NM_002190.3:c.*159G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 51 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
IL17A	NM_002190.3	c.*159G>A		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.*159G>A		3_prime_UTR_variant	Exon 3 of 3		NM_002190.3	ENSP00000497968.1

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

African (AFR) AF: 0.0934 AC: 1096 AN: 11734

American (AMR) AF: 0.148 AC: 2281 AN: 15448

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 3257 AN: 13108

East Asian (EAS) AF: 0.000370 AC: 11 AN: 29714

South Asian (SAS) AF: 0.150 AC: 5496 AN: 36580

European-Finnish (FIN) AF: 0.204 AC: 5957 AN: 29198

Middle Eastern (MID) AF: 0.249 AC: 473 AN: 1896

European-Non Finnish (NFE) AF: 0.234 AC: 59924 AN: 256254

Other (OTH) AF: 0.210 AC: 5194 AN: 24780

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

African (AFR) AF: 0.0978 AC: 4062 AN: 41524

American (AMR) AF: 0.181 AC: 2758 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.134 AC: 644 AN: 4818

European-Finnish (FIN) AF: 0.202 AC: 2132 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16118 AN: 67982

Other (OTH) AF: 0.217 AC: 456 AN: 2106

Alfa AF: 0.213 Hom.: 5796

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

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7747909; hg19: chr6-52054249;