rs189630805

Variant names:

• chr6-52236808-G-A
• rs189630805
• ENST00000478427.1:n.799C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52236808-G-A
• chr6-52236808-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000478427.1(IL17F):​n.799C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 798,730 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0084 (9 hom., cov: 32)
  • Exomes 𝑓: 0.010 (46 hom.)
• Consequence: IL17F ENST00000478427.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.454
• Publications: 1 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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd4 at 1280 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17F	NM_052872.4	c.*123C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1	c.*123C>T		3_prime_UTR_variant	Exon 4 of 4		XP_011512578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17F	ENST00000478427.1	n.799C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
IL17F	ENST00000336123.5	c.*123C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_052872.4	ENSP00000337432.4
IL17F	ENST00000699946.1	c.*123C>T		3_prime_UTR_variant	Exon 4 of 4			ENSP00000514702.1

Frequencies

GnomAD3 genomes AF: 0.00841 AC: 1279 AN: 152118 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.0100 AC: 6497 AN: 646494 Hom.: 46 Cov.: 7 AF XY: 0.00975 AC XY: 3418 AN XY: 350570

African (AFR) AF: 0.00189 AC: 34 AN: 18018

American (AMR) AF: 0.00371 AC: 162 AN: 43628

Ashkenazi Jewish (ASJ) AF: 0.00223 AC: 47 AN: 21054

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 36012

South Asian (SAS) AF: 0.00299 AC: 207 AN: 69256

European-Finnish (FIN) AF: 0.0238 AC: 1173 AN: 49340

Middle Eastern (MID) AF: 0.000733 AC: 2 AN: 2730

European-Non Finnish (NFE) AF: 0.0123 AC: 4603 AN: 372808

Other (OTH) AF: 0.00796 AC: 268 AN: 33648

GnomAD4 genome AF: 0.00841 AC: 1280 AN: 152236 Hom.: 9 Cov.: 32 AF XY: 0.00824 AC XY: 613 AN XY: 74432

African (AFR) AF: 0.00229 AC: 95 AN: 41542

American (AMR) AF: 0.00471 AC: 72 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4818

European-Finnish (FIN) AF: 0.0194 AC: 205 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 859 AN: 68014

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00921 Hom.: 0

Bravo AF: 0.00712

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Candidiasis, familial, 6 Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.55
DANN	Benign	0.58
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism

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: rs189630805; hg19: chr6-52101606; COSMIC: COSV60233639;