chr6-52238931-G-A

Position:

chr6-52238931-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_052872.4(IL17F):c.53C>T(p.Ser18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,613,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S18S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

IL17F
NM_052872.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.54

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010596454).

BP6

Variant 6-52238931-G-A is Benign according to our data. Variant chr6-52238931-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 582871.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17F	NM_052872.4 linkuse as main transcript	c.53C>T	p.Ser18Leu	missense_variant	2/3	ENST00000336123.5
IL17F	XM_011514276.1 linkuse as main transcript	c.53C>T	p.Ser18Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IL17F	ENST00000336123.5 linkuse as main transcript	c.53C>T	p.Ser18Leu	missense_variant	2/3	1	NM_052872.4	P1
IL17F	ENST00000478427.1 linkuse as main transcript	n.237C>T		non_coding_transcript_exon_variant	1/2	1
IL17F	ENST00000699946.1 linkuse as main transcript	c.53C>T	p.Ser18Leu	missense_variant	3/4			P1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000211

AC:

AN:

250964

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000103

AC:

150

AN:

1461042

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

AF:

0.000414

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000703

Hom.:

Bravo

AF:

0.000434

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Candidiasis, familial, 6

Uncertain:1

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 18 of the IL17F protein (p.Ser18Leu). This variant is present in population databases (rs145598353, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with IL17F-related conditions. ClinVar contains an entry for this variant (Variation ID: 582871). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.1

DANN

Benign

0.39

DEOGEN2

Benign

0.054

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.49

M_CAP

Benign

0.0044

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

1.5

REVEL

Benign

0.058

Sift

Benign

1.0

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.18

MVP

0.23

MPC

0.091

ClinPred

0.0088

GERP RS

2.1

Varity_R

0.023

gMVP

0.46

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