6-52236941-T-C

Position:

chr6-52236941-T-C

Variant summary

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

The NM_052872.4(IL17F):c.482A>G(p.His161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,613,046 control chromosomes in the GnomAD database, including 2,997 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 390 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2607 hom. )

Consequence

IL17F
NM_052872.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.761

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=0.0018661618).

BP6

Variant 6-52236941-T-C is Benign according to our data. Variant chr6-52236941-T-C is described in ClinVar as [Benign]. Clinvar id is 357466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52236941-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 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.482A>G	p.His161Arg	missense_variant	3/3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1 linkuse as main transcript	c.482A>G	p.His161Arg	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.482A>G	p.His161Arg	missense_variant	3/3	1	NM_052872.4	ENSP00000337432	P1
IL17F	ENST00000478427.1 linkuse as main transcript	n.666A>G		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1 linkuse as main transcript	c.482A>G	p.His161Arg	missense_variant	4/4			ENSP00000514702	P1

Frequencies

GnomAD3 genomes

AF:

0.0665

AC:

10118

AN:

152120

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0831

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0773

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0672

AC:

16859

AN:

250950

Hom.:

667

AF XY:

0.0676

AC XY:

9174

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.0868

Gnomad AMR exome

AF:

0.0451

Gnomad ASJ exome

AF:

0.0449

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.0739

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.0504

Gnomad OTH exome

AF:

0.0556

GnomAD4 exome

AF:

0.0548

AC:

80034

AN:

1460808

Hom.:

2607

Cov.:

AF XY:

0.0551

AC XY:

40067

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.0839

Gnomad4 AMR exome

AF:

0.0453

Gnomad4 ASJ exome

AF:

0.0421

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.0714

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0480

Gnomad4 OTH exome

AF:

0.0616

GnomAD4 genome

AF:

0.0665

AC:

10123

AN:

152238

Hom.:

390

Cov.:

AF XY:

0.0701

AC XY:

5214

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0830

Gnomad4 AMR

AF:

0.0484

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0770

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.0484

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0508

Hom.:

478

Bravo

AF:

0.0612

TwinsUK

AF:

0.0394

AC:

146

ALSPAC

AF:

0.0532

AC:

205

ESP6500AA

AF:

0.0897

AC:

395

ESP6500EA

AF:

0.0494

AC:

425

ExAC

AF:

0.0668

AC:

8112

Asia WGS

AF:

0.107

AC:

372

AN:

3478

EpiCase

AF:

0.0450

EpiControl

AF:

0.0462

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

This variant is associated with the following publications: (PMID: 22812194, 24164796, 31616423, 31831764, 20620187, 24440568, 16630936, 20618772, 24829928, 22579472, 21615796) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.2

DANN

Benign

0.60

DEOGEN2

Benign

0.27

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.066

Sift

Benign

0.19

Sift4G

Benign

0.13

Polyphen

0.048

Vest4

0.010

MPC

0.13

ClinPred

0.0043

GERP RS

2.8

Varity_R

0.32

gMVP

0.56

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