dbSNP rs41525346: FLCN:c.396+59T>C (chr17-17226117-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144997.7(FLCN):c.396+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 1,605,736 control chromosomes in the GnomAD database, including 5,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 381 hom., cov: 32)

Exomes 𝑓: 0.080 ( 4991 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.970

Variant links:

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]

FLCN links:

ENSG00000264187 (HGNC:):

ENSG00000264187 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-17226117-A-G is Benign according to our data. Variant chr17-17226117-A-G is described in ClinVar as [Benign]. Clinvar id is 41858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226117-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7 link	c.396+59T>C		intron_variant	Intron 5 of 13	ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9 link	c.396+59T>C		intron_variant	Intron 5 of 13	1	NM_144997.7	ENSP00000285071.4		Q8NFG4-1
ENSG00000264187	ENST00000427497.3 link	n.148+1873T>C		intron_variant	Intron 4 of 11	1		ENSP00000394249.3		J3QW42

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9564

AN:

152062

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0955

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0854

Gnomad FIN

AF:

0.0631

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0839

Gnomad OTH

AF:

0.0842

GnomAD3 exomes

AF:

0.0768

AC:

18722

AN:

243898

Hom.:

895

AF XY:

0.0796

AC XY:

10541

AN XY:

132418

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0956

Gnomad FIN exome

AF:

0.0620

Gnomad NFE exome

AF:

0.0822

Gnomad OTH exome

AF:

0.0901

GnomAD4 exome

AF:

0.0795

AC:

115595

AN:

1453556

Hom.:

4991

Cov.:

AF XY:

0.0806

AC XY:

58295

AN XY:

722984

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.0998

Gnomad4 FIN exome

AF:

0.0645

Gnomad4 NFE exome

AF:

0.0814

Gnomad4 OTH exome

AF:

0.0787

GnomAD4 genome

AF:

0.0628

AC:

9560

AN:

152180

Hom.:

381

Cov.:

AF XY:

0.0635

AC XY:

4721

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0954

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0857

Gnomad4 FIN

AF:

0.0631

Gnomad4 NFE

AF:

0.0839

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0762

Hom.:

196

Bravo

AF:

0.0619

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2012

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Birt-Hogg-Dube syndrome

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

DANN

Benign

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over