6-52236941-T-C

Variant names:

• chr6-52236941-T-C
• rs763780
• NM_052872.4:c.482A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 417 publications found

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 Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• candidiasis, familial, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LOC124901328 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.
• 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 rank	MANE	Protein	UniProt
IL17F	NM_052872.4	c.482A>G	p.His161Arg	missense_variant	Exon 3 of 3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1	c.482A>G	p.His161Arg	missense_variant	Exon 4 of 4		XP_011512578.1
LOC124901328	XR_007059607.1	n.-145T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17F	ENST00000336123.5	c.482A>G	p.His161Arg	missense_variant	Exon 3 of 3	1	NM_052872.4	ENSP00000337432.4
IL17F	ENST00000478427.1	n.666A>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
IL17F	ENST00000699946.1	c.482A>G	p.His161Arg	missense_variant	Exon 4 of 4			ENSP00000514702.1

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

GnomAD2 exomes AF: 0.0672 AC: 16859 AN: 250950 AF XY: 0.0676

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 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

African (AFR) AF: 0.0839 AC: 2809 AN: 33464

American (AMR) AF: 0.0453 AC: 2027 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 1100 AN: 26128

East Asian (EAS) AF: 0.130 AC: 5145 AN: 39694

South Asian (SAS) AF: 0.0714 AC: 6160 AN: 86232

European-Finnish (FIN) AF: 0.103 AC: 5515 AN: 53408

Middle Eastern (MID) AF: 0.0436 AC: 251 AN: 5762

European-Non Finnish (NFE) AF: 0.0480 AC: 53307 AN: 1111030

Other (OTH) AF: 0.0616 AC: 3720 AN: 60368

GnomAD4 genome AF: 0.0665 AC: 10123 AN: 152238 Hom.: 390 Cov.: 32 AF XY: 0.0701 AC XY: 5214 AN XY: 74432

African (AFR) AF: 0.0830 AC: 3449 AN: 41538

American (AMR) AF: 0.0484 AC: 740 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.148 AC: 765 AN: 5180

South Asian (SAS) AF: 0.0770 AC: 371 AN: 4820

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3291 AN: 68012

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0534 Hom.: 1095

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

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.76
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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