6-52236960-C-T

Position:

chr6-52236960-C-T

Variant summary

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

The NM_052872.4(IL17F):c.463G>A(p.Val155Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0427 in 1,613,836 control chromosomes in the GnomAD database, including 1,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 107 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1663 hom. )

Consequence

IL17F
NM_052872.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 5.34

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:

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=0.0039727986).

BP6

Variant 6-52236960-C-T is Benign according to our data. Variant chr6-52236960-C-T is described in ClinVar as [Benign]. Clinvar id is 357468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52236960-C-T is described in Lovd as [Benign]. Variant chr6-52236960-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17F	NM_052872.4 linkuse as main transcript	c.463G>A	p.Val155Ile	missense_variant	3/3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1 linkuse as main transcript	c.463G>A	p.Val155Ile	missense_variant	4/4		XP_011512578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IL17F	ENST00000336123.5 linkuse as main transcript	c.463G>A	p.Val155Ile	missense_variant	3/3	1	NM_052872.4	ENSP00000337432	P1
IL17F	ENST00000478427.1 linkuse as main transcript	n.647G>A		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1 linkuse as main transcript	c.463G>A	p.Val155Ile	missense_variant	4/4			ENSP00000514702	P1

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4608

AN:

152104

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00833

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0510

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0304

AC:

7630

AN:

251040

Hom.:

169

AF XY:

0.0307

AC XY:

4169

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00640

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00207

Gnomad SAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.0504

Gnomad NFE exome

AF:

0.0454

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0440

AC:

64248

AN:

1461614

Hom.:

1663

Cov.:

AF XY:

0.0431

AC XY:

31310

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00651

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0125

Gnomad4 EAS exome

AF:

0.00731

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.0514

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0303

AC:

4605

AN:

152222

Hom.:

107

Cov.:

AF XY:

0.0291

AC XY:

2167

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00831

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0510

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0392

Hom.:

186

Bravo

AF:

0.0268

TwinsUK

AF:

0.0510

AC:

189

ALSPAC

AF:

0.0415

AC:

160

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0440

AC:

378

ExAC

AF:

0.0304

AC:

3692

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0384

EpiControl

AF:

0.0413

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

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	Jan 13, 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 provided

Benign:1Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

IL17F-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.93

REVEL

Benign

0.18

Sift

Uncertain

0.024

Sift4G

Benign

0.085

Polyphen

0.99

Vest4

0.13

MPC

0.40

ClinPred

0.015

GERP RS

5.7

Varity_R

0.64

gMVP

0.71

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