chr6-52236795-T-C

Position:

• chr6-52236795-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_052872.4(IL17F):​c.*136A>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 0.00445 in 771,892 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (22 hom.)
• Consequence: IL17F NM_052872.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.262

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-52236795-T-C is Benign according to our data. Variant chr6-52236795-T-C is described in ClinVar as [Benign]. Clinvar id is 357464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2136/152378) while in subpopulation AFR AF= 0.0479 (1990/41588). AF 95% confidence interval is 0.0461. There are 42 homozygotes in gnomad4. There are 955 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2136 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17F	NM_052872.4	c.*136A>G		3_prime_UTR_variant	3/3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1	c.*136A>G		3_prime_UTR_variant	4/4		XP_011512578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17F	ENST00000336123.5	c.*136A>G		3_prime_UTR_variant	3/3	1	NM_052872.4	ENSP00000337432	P1
IL17F	ENST00000478427.1	n.812A>G		non_coding_transcript_exon_variant	2/2	1
IL17F	ENST00000699946.1	c.*136A>G		3_prime_UTR_variant	4/4			ENSP00000514702	P1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2134 AN: 152260 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00210 AC: 1301 AN: 619514 Hom.: 22 Cov.: 6 AF XY: 0.00175 AC XY: 588 AN XY: 336014

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.00386

Gnomad4 ASJ exome AF: 0.000637

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000455

Gnomad4 OTH exome AF: 0.00413

GnomAD4 genome AF: 0.0140 AC: 2136 AN: 152378 Hom.: 42 Cov.: 32 AF XY: 0.0128 AC XY: 955 AN XY: 74520

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0112 Hom.: 8

Bravo AF: 0.0165

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Candidiasis, familial, 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.84
CADD	Benign	2.2
DANN	Benign	0.69

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: rs11465554; hg19: chr6-52101593;