rs117796773

chr6-52238729-C-Achr6-52238729-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_052872.4(IL17F):c.254+1G>T variant causes a splice donor change. The variant allele was found at a frequency of 0.000537 in 1,611,986 control chromosomes in the GnomAD database, including 9 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (9 hom.)
• Consequence: IL17F NM_052872.4 splice_donor
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 4.51

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]

LOC124901328 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 6-52238729-C-A is Benign according to our data. Variant chr6-52238729-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 225391.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
• BS2: High AC in GnomAd at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17F	NM_052872.4	c.254+1G>T		splice_donor_variant		ENST00000336123.5
LOC124901328	XR_007059607.1	n.251-13C>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
IL17F	XM_011514276.1	c.254+1G>T		splice_donor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17F	ENST00000336123.5	c.254+1G>T		splice_donor_variant		1	NM_052872.4	P1
IL17F	ENST00000478427.1	n.438+1G>T		splice_donor_variant, non_coding_transcript_variant		1
IL17F	ENST00000699946.1	c.254+1G>T		splice_donor_variant				P1

Frequencies

GnomAD3 genomes AF: 0.000670 AC: 102 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00139 AC: 348 AN: 251098 Hom.: 1 AF XY: 0.00139 AC XY: 188 AN XY: 135730

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0137

Gnomad SAS exome AF: 0.00147

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000525 AC: 766 AN: 1459682 Hom.: 9 Cov.: 30 AF XY: 0.000555 AC XY: 403 AN XY: 726320

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0114

Gnomad4 SAS exome AF: 0.00198

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000631

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.000779 AC XY: 58 AN XY: 74466

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000342 Hom.: 0

Bravo AF: 0.00104

ExAC AF: 0.00136 AC: 165

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Candidiasis, familial, 6 Uncertain:1 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 13, 2018	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Uncertain significance, criteria provided, single submitter	reference population	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	Mar 18, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 08, 2024	- -

not provided Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.40
Cadd	Pathogenic	33
Dann	Uncertain	0.99
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Uncertain	0.93	D
MutationTaster	Benign	1.0	D
GERP RS		5.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_DL_spliceai		1.0		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs117796773; hg19: chr6-52103527; COSMIC: COSV60235296;