rs41323249

Positions:

• chr17-17220853-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_144606.7(FLCN):​c.*526G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 224,338 control chromosomes in the GnomAD database, including 3,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2346 hom., cov: 32)
  • Exomes 𝑓: 0.13 (778 hom.)
• Consequence: FLCN NM_144606.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-17220853-C-T is Benign according to our data. Variant chr17-17220853-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7	c.871+684G>A		intron_variant		ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.871+684G>A		intron_variant		1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.149-1799G>A		intron_variant		1		ENSP00000394249.3
FLCN	ENST00000466317.1	n.1398G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25992 AN: 152016 Hom.: 2342 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.128 AC: 9258 AN: 72204 Hom.: 778 Cov.: 0 AF XY: 0.127 AC XY: 4783 AN XY: 37582

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.00565

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0889

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.171 AC: 26018 AN: 152134 Hom.: 2346 Cov.: 32 AF XY: 0.169 AC XY: 12582 AN XY: 74384

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.188

Alfa AF: 0.172 Hom.: 475

Bravo AF: 0.176

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.50

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: rs41323249; hg19: chr17-17124167;