chr6-52236688-A-C

Position:

• chr6-52236688-A-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.*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

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 (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/exons	MANE	UniProt
IL17F	NM_052872.4	c.*243T>G		3_prime_UTR_variant	3/3	ENST00000336123.5
IL17F	XM_011514276.1	c.*243T>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17F	ENST00000336123.5	c.*243T>G		3_prime_UTR_variant	3/3	1	NM_052872.4	P1
IL17F	ENST00000478427.1	n.919T>G		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1	c.*243T>G		3_prime_UTR_variant	4/4			P1

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

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.0000500

Gnomad4 SAS exome AF: 0.0632

Gnomad4 FIN exome AF: 0.0887

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0603

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

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0391

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0532

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.0624

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0545 Hom.: 112

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2021

- -

Candidiasis, familial, 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.72

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: rs1953325; hg19: chr6-52101486;