Variant rs3819025 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002190.3(IL17A):c.27+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 1,612,372 control chromosomes in the GnomAD database, including 9,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 1118 hom., cov: 33)

Exomes 𝑓: 0.072 ( 8168 hom. )

Consequence

IL17A
NM_002190.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.868

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 6-52186476-G-A is Benign according to our data. Variant chr6-52186476-G-A is described in ClinVar as [Benign]. Clinvar id is 1273159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17A	NM_002190.3 link	c.27+18G>A		intron_variant	Intron 1 of 2	ENST00000648244.1	NP_002181.1	Q16552

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17A	ENST00000648244.1 link	c.27+18G>A		intron_variant	Intron 1 of 2		NM_002190.3	ENSP00000497968.1		Q16552

Frequencies

GnomAD3 genomes

AF:

0.0889

AC:

13520

AN:

152154

Hom.:

1105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0503

Gnomad OTH

AF:

0.0903

GnomAD3 exomes

AF:

0.128

AC:

32108

AN:

250576

Hom.:

4518

AF XY:

0.117

AC XY:

15805

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.0741

Gnomad AMR exome

AF:

0.431

Gnomad ASJ exome

AF:

0.0533

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.0286

Gnomad NFE exome

AF:

0.0516

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0720

AC:

105093

AN:

1460100

Hom.:

8168

Cov.:

AF XY:

0.0730

AC XY:

53021

AN XY:

726376

show subpopulations

Gnomad4 AFR exome

AF:

0.0733

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.0574

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.0483

Gnomad4 OTH exome

AF:

0.0787

GnomAD4 genome

AF:

0.0890

AC:

13558

AN:

152272

Hom.:

1118

Cov.:

AF XY:

0.0936

AC XY:

6968

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0751

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.0503

Gnomad4 OTH

AF:

0.0974

Alfa

AF:

0.0700

Hom.:

1049

Bravo

AF:

0.107

Asia WGS

AF:

0.215

AC:

748

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.91

DANN

Benign

0.76

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