rs41356848

chr17-17222388-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_144997.7(FLCN):c.779+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,465,784 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (40 hom., cov: 32)
  • Exomes 𝑓: 0.020 (342 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-17222388-G-A is Benign according to our data. Variant chr17-17222388-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0163 (2475/152288) while in subpopulation AMR AF= 0.0286 (438/15290). AF 95% confidence interval is 0.0264. There are 40 homozygotes in gnomad4. There are 1193 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLCN	NM_144997.7	c.779+113C>T		intron_variant		ENST00000285071.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLCN	ENST00000285071.9	c.779+113C>T		intron_variant		1	NM_144997.7	P1
FLCN	ENST00000389169.9	c.779+113C>T		intron_variant		1
FLCN	ENST00000466317.1	n.622+113C>T		intron_variant, non_coding_transcript_variant		2
FLCN	ENST00000480316.1	n.745+113C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2470 AN: 152170 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0204 AC: 26739 AN: 1313496 Hom.: 342 AF XY: 0.0199 AC XY: 13011 AN XY: 654298

Gnomad4 AFR exome AF: 0.00325

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00794

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0225

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0163 AC: 2475 AN: 152288 Hom.: 40 Cov.: 32 AF XY: 0.0160 AC XY: 1193 AN XY: 74448

Gnomad4 AFR AF: 0.00496

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0175 Hom.: 8

Bravo AF: 0.0164

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs41356848; hg19: chr17-17125702;