rs1736215

Positions:

• chr17-17228888-G-A
• chr17-17228888-G-C
• chr17-17228888-G-T

Variant summary

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

The NM_001353230.2(FLCN):​c.-290C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,160 control chromosomes in the GnomAD database, including 21,253 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 0.52 (21224 hom., cov: 32)
  • Exomes 𝑓: 0.55 (29 hom.)
• Consequence: FLCN NM_001353230.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

Genes affected

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]

ENSG00000264187 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7	c.-24-727C>T		intron_variant		ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.-24-727C>T		intron_variant		1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.-24-727C>T		intron_variant		1		ENSP00000394249.3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78508 AN: 151894 Hom.: 21221 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.554 AC: 82 AN: 148 Hom.: 29 Cov.: 0 AF XY: 0.554 AC XY: 51 AN XY: 92

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.857

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.517 AC: 78527 AN: 152012 Hom.: 21224 Cov.: 32 AF XY: 0.523 AC XY: 38817 AN XY: 74290

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.479

Alfa AF: 0.536 Hom.: 2783

Bravo AF: 0.499

Asia WGS AF: 0.573 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1736215; hg19: chr17-17132202;