6-52237139-G-A

Position:

chr6-52237139-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_052872.4(IL17F):c.284C>T(p.Ser95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

IL17F
NM_052872.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 0.699

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:

IL17F (HGNC:):

IL17F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17F	NM_052872.4 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	3/3	ENST00000336123.5	NP_443104.1	Q96PD4
IL17F	XM_011514276.1 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	4/4		XP_011512578.1	Q96PD4
LOC124901328	XR_007059607.1 linkuse as main transcript	n.54G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17F	ENST00000336123.5 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	3/3	1	NM_052872.4	ENSP00000337432.4	Q96PD4
IL17F	ENST00000478427.1 linkuse as main transcript	n.468C>T		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	4/4			ENSP00000514702.1	Q96PD4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250750

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 6

Pathogenic:1Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 01, 2011	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2024	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 95 of the IL17F protein (p.Ser95Leu). This variant is present in population databases (rs748486078, gnomAD 0.02%). This missense change has been observed in individual(s) with mucocutaneous candidiasis (PMID: 21350122). This variant is also known as p.Ser65Leu. ClinVar contains an entry for this variant (Variation ID: 30589). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects IL17F function (PMID: 21350122, 34587561). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Benign

0.014

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.28

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.31

Sift

Benign

0.046

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.69

MutPred

0.49

Loss of disorder (P = 0.0735);

MVP

0.64

MPC

0.33

ClinPred

0.70

GERP RS

3.7

Varity_R

0.50

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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