6-52236688-A-C

Variant names:

• chr6-52236688-A-C
• rs1953325
• ENST00000478427.1:n.919T>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.*243T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 465,872 control chromosomes in the GnomAD database, including 1,037 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (265 hom., cov: 32)
  • Exomes 𝑓: 0.062 (772 hom.)
• Consequence: IL17F NM_052872.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.347
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-52236688-A-C is Benign according to our data. Variant chr6-52236688-A-C is described in ClinVar as [Benign]. Clinvar id is 357463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17F	NM_052872.4	c.*243T>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1	c.*243T>G		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.919T>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
IL17F	ENST00000336123.5	c.*243T>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_052872.4	ENSP00000337432.4
IL17F	ENST00000699946.1	c.*243T>G		3_prime_UTR_variant	Exon 4 of 4			ENSP00000514702.1

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7490 AN: 152218 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.0616 AC: 19304 AN: 313536 Hom.: 772 Cov.: 0 AF XY: 0.0623 AC XY: 10330 AN XY: 165820

African (AFR) AF: 0.0213 AC: 209 AN: 9832

American (AMR) AF: 0.0344 AC: 482 AN: 14026

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 1292 AN: 10108

East Asian (EAS) AF: 0.0000500 AC: 1 AN: 20016

South Asian (SAS) AF: 0.0632 AC: 2185 AN: 34554

European-Finnish (FIN) AF: 0.0887 AC: 1349 AN: 15210

Middle Eastern (MID) AF: 0.0776 AC: 109 AN: 1404

European-Non Finnish (NFE) AF: 0.0661 AC: 12577 AN: 190136

Other (OTH) AF: 0.0603 AC: 1100 AN: 18250

GnomAD4 genome AF: 0.0492 AC: 7490 AN: 152336 Hom.: 265 Cov.: 32 AF XY: 0.0499 AC XY: 3713 AN XY: 74480

African (AFR) AF: 0.0190 AC: 791 AN: 41582

American (AMR) AF: 0.0391 AC: 598 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0532 AC: 257 AN: 4830

European-Finnish (FIN) AF: 0.0841 AC: 892 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0624 AC: 4245 AN: 68028

Other (OTH) AF: 0.0540 AC: 114 AN: 2112

Alfa AF: 0.0551 Hom.: 130

Bravo AF: 0.0449

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.83
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		0.35
Mutation Taster		=100/0	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: rs1953325; hg19: chr6-52101486;