6-52236941-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. H161H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.066 (390 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2607 hom.)
• Consequence: IL17F NM_052872.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.761

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]

ACMG classification

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	UniProt
IL17F	NM_052872.4	c.482A>G	p.His161Arg	missense_variant	3/3	ENST00000336123.5
IL17F	XM_011514276.1	c.482A>G	p.His161Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17F	ENST00000336123.5	c.482A>G	p.His161Arg	missense_variant	3/3	1	NM_052872.4	P1
IL17F	ENST00000478427.1	n.666A>G		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1	c.482A>G	p.His161Arg	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10118 AN: 152120 Hom.: 393 Cov.: 32

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

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.: 30 AF XY: 0.0551 AC XY: 40067 AN XY: 726828

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.: 32 AF XY: 0.0701 AC XY: 5214 AN XY: 74432

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

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	Invitae	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	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	4.2
Dann	Benign	0.60
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.066
Sift	Benign	0.19	T
Sift4G	Benign	0.13	T
Polyphen		0.048	B
Vest4		0.010
MPC		0.13
ClinPred		0.0043	T
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

Other links and lift over

dbSNP: rs763780; hg19: chr6-52101739; COSMIC: COSV60233806;