NM_052872.4:c.377A>G

Variant names:

• chr6-52237046-T-C
• rs2397084
• NM_052872.4:c.377A>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.377A>G​(p.Glu126Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0814 in 1,614,210 control chromosomes in the GnomAD database, including 6,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (400 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5624 hom.)
• Consequence: IL17F NM_052872.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.41
• Publications: 99 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)

LOC124901328 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037688613).
• BP6: Variant 6-52237046-T-C is Benign according to our data. Variant chr6-52237046-T-C is described in ClinVar as Benign. ClinVar VariationId is 357469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052872.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17F	NM_052872.4	MANE Select	c.377A>G	p.Glu126Gly	missense	Exon 3 of 3	NP_443104.1	Q96PD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17F	ENST00000336123.5	TSL:1 MANE Select	c.377A>G	p.Glu126Gly	missense	Exon 3 of 3	ENSP00000337432.4	Q96PD4
	IL17F	ENST00000478427.1	TSL:1	n.561A>G		non_coding_transcript_exon	Exon 2 of 2
	IL17F	ENST00000699946.1		c.377A>G	p.Glu126Gly	missense	Exon 4 of 4	ENSP00000514702.1	Q96PD4

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9312 AN: 152230 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.00826

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.0531

GnomAD2 exomes AF: 0.0665 AC: 16711 AN: 251256 AF XY: 0.0693

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.0304

Gnomad ASJ exome AF: 0.0445

Gnomad EAS exome AF: 0.00849

Gnomad FIN exome AF: 0.0645

Gnomad NFE exome AF: 0.0958

Gnomad OTH exome AF: 0.0716

GnomAD4 exome AF: 0.0836 AC: 122144 AN: 1461862 Hom.: 5624 Cov.: 32 AF XY: 0.0835 AC XY: 60750 AN XY: 727234

African (AFR) AF: 0.0143 AC: 478 AN: 33480

American (AMR) AF: 0.0315 AC: 1410 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 1190 AN: 26136

East Asian (EAS) AF: 0.00935 AC: 371 AN: 39698

South Asian (SAS) AF: 0.0682 AC: 5885 AN: 86254

European-Finnish (FIN) AF: 0.0668 AC: 3566 AN: 53418

Middle Eastern (MID) AF: 0.0952 AC: 549 AN: 5768

European-Non Finnish (NFE) AF: 0.0938 AC: 104341 AN: 1111988

Other (OTH) AF: 0.0721 AC: 4354 AN: 60396

GnomAD4 genome AF: 0.0611 AC: 9310 AN: 152348 Hom.: 400 Cov.: 32 AF XY: 0.0598 AC XY: 4454 AN XY: 74498

African (AFR) AF: 0.0180 AC: 750 AN: 41580

American (AMR) AF: 0.0466 AC: 714 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3472

East Asian (EAS) AF: 0.00809 AC: 42 AN: 5194

South Asian (SAS) AF: 0.0615 AC: 297 AN: 4828

European-Finnish (FIN) AF: 0.0611 AC: 649 AN: 10620

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6447 AN: 68026

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0842 Hom.: 2072

Bravo AF: 0.0571

TwinsUK AF: 0.104 AC: 384

ALSPAC AF: 0.0955 AC: 368

ESP6500AA AF: 0.0216 AC: 95

ESP6500EA AF: 0.0898 AC: 772

ExAC AF: 0.0686 AC: 8326

Asia WGS AF: 0.0340 AC: 121 AN: 3478

EpiCase AF: 0.0925

EpiControl AF: 0.0909

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Candidiasis, familial, 6 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.24
MPC		0.56
ClinPred		0.031	T
GERP RS		5.7
Varity_R		0.91
gMVP		0.74
Mutation Taster		=82/18	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2397084; hg19: chr6-52101844; COSMIC: COSV60233930;