rs11465554

Variant names:

• chr6-52236795-T-C
• rs11465554
• ENST00000478427.1:n.812A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2136 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17F	NM_052872.4	c.*136A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000336123.5	NP_443104.1
IL17F	XM_011514276.1	c.*136A>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.812A>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
IL17F	ENST00000336123.5	c.*136A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_052872.4	ENSP00000337432.4
IL17F	ENST00000699946.1	c.*136A>G		3_prime_UTR_variant	Exon 4 of 4			ENSP00000514702.1

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

African (AFR) AF: 0.0466 AC: 815 AN: 17506

American (AMR) AF: 0.00386 AC: 165 AN: 42778

Ashkenazi Jewish (ASJ) AF: 0.000637 AC: 13 AN: 20418

East Asian (EAS) AF: 0.00 AC: 0 AN: 35760

South Asian (SAS) AF: 0.000103 AC: 7 AN: 67728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46464

Middle Eastern (MID) AF: 0.00195 AC: 5 AN: 2566

European-Non Finnish (NFE) AF: 0.000455 AC: 161 AN: 353610

Other (OTH) AF: 0.00413 AC: 135 AN: 32684

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

African (AFR) AF: 0.0479 AC: 1990 AN: 41588

American (AMR) AF: 0.00601 AC: 92 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68038

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.00919 Hom.: 11

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

Jan 12, 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	-0.84
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		0.26
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: rs11465554; hg19: chr6-52101593;