Variant chr6-52189451-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.147

Variant links:

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]

IL17A links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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.:

AF XY:

0.199

AC XY:

43391

AN XY:

217974

show subpopulations

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.:

AF XY:

0.177

AC XY:

13142

AN XY:

74382

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over