rs2397084

Positions:

chr6-52237046-T-C

Variant summary

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

The ENST00000336123.5(IL17F):c.377A>G(p.Glu126Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0814 in 1,614,210 control chromosomes in the GnomAD database, including 6,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 400 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5624 hom. )

Consequence

IL17F
ENST00000336123.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.41

Variant links:

Genes affected

IL17F (HGNC:16404): (interleukin 17F) The protein encoded by this gene is a cytokine that shares sequence similarity with IL17. This cytokine is expressed by activated T cells, and has been shown to stimulate the production of several other cytokines, including IL6, IL8, and CSF2/GM_CSF. This cytokine is also found to inhibit the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1. [provided by RefSeq, Jul 2008]

IL17F links:

LOC124901328 (HGNC:):

LOC124901328 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 (MetaRNN=0.0037688613).

BP6

Variant 6-52237046-T-C is Benign according to our data. Variant chr6-52237046-T-C is described in ClinVar as [Benign]. Clinvar id is 357469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52237046-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL17F	NM_052872.4 linkuse as main transcript	c.377A>G	p.Glu126Gly	missense_variant	3/3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1 linkuse as main transcript	c.377A>G	p.Glu126Gly	missense_variant	4/4		XP_011512578.1
LOC124901328	XR_007059607.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IL17F	ENST00000336123.5 linkuse as main transcript	c.377A>G	p.Glu126Gly	missense_variant	3/3	1	NM_052872.4	ENSP00000337432	P1
IL17F	ENST00000478427.1 linkuse as main transcript	n.561A>G		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1 linkuse as main transcript	c.377A>G	p.Glu126Gly	missense_variant	4/4			ENSP00000514702	P1

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

9312

AN:

152230

Hom.:

400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.0468

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.00826

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0611

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0948

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0665

AC:

16711

AN:

251256

Hom.:

705

AF XY:

0.0693

AC XY:

9409

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.0445

Gnomad EAS exome

AF:

0.00849

Gnomad SAS exome

AF:

0.0674

Gnomad FIN exome

AF:

0.0645

Gnomad NFE exome

AF:

0.0958

Gnomad OTH exome

AF:

0.0716

GnomAD4 exome

AF:

0.0836

AC:

122144

AN:

1461862

Hom.:

5624

Cov.:

AF XY:

0.0835

AC XY:

60750

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.0315

Gnomad4 ASJ exome

AF:

0.0455

Gnomad4 EAS exome

AF:

0.00935

Gnomad4 SAS exome

AF:

0.0682

Gnomad4 FIN exome

AF:

0.0668

Gnomad4 NFE exome

AF:

0.0938

Gnomad4 OTH exome

AF:

0.0721

GnomAD4 genome

AF:

0.0611

AC:

9310

AN:

152348

Hom.:

400

Cov.:

AF XY:

0.0598

AC XY:

4454

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.0429

Gnomad4 EAS

AF:

0.00809

Gnomad4 SAS

AF:

0.0615

Gnomad4 FIN

AF:

0.0611

Gnomad4 NFE

AF:

0.0948

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0845

Hom.:

856

Bravo

AF:

0.0571

TwinsUK

AF:

0.104

AC:

384

ALSPAC

AF:

0.0955

AC:

368

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.0898

AC:

772

ExAC

AF:

0.0686

AC:

8326

Asia WGS

AF:

0.0340

AC:

121

AN:

3478

EpiCase

AF:

0.0925

EpiControl

AF:

0.0909

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 6

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2021

This variant is associated with the following publications: (PMID: 30290665, 18769923, 20618772) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.77

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.19

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.24

MPC

0.56

ClinPred

0.031

GERP RS

5.7

Varity_R

0.91

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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