17-17237369-A-G

Position:

• chr17-17237369-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.779 in 152,108 control chromosomes in the GnomAD database, including 46,338 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46338 hom., cov: 32)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

Genes affected

(HGNC:):

FLCN (HGNC:27310): (folliculin) This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.17237369A>G		intergenic_region
FLCN	XM_047435531.1	c.-449T>C		upstream_gene_variant			XP_047291487.1
FLCN	XM_047435536.1	c.-449T>C		upstream_gene_variant			XP_047291492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118470 AN: 151990 Hom.: 46317 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.779 AC: 118550 AN: 152108 Hom.: 46338 Cov.: 32 AF XY: 0.784 AC XY: 58305 AN XY: 74360

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.758

Alfa AF: 0.753 Hom.: 3553

Bravo AF: 0.773

Asia WGS AF: 0.807 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1736208; hg19: chr17-17140683;