rs41525346

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

Birt-Hogg-Dube syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
Birt-Hogg-Dube syndrome 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
familial spontaneous pneumothorax
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics
renal carcinoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
colorectal cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

FLCN links:

ENSG00000264187 (HGNC:):

ENSG00000264187 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.023).

BP6

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

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

GnomAD2 exomes

AF:

0.0768

AC:

18722

AN:

243898

AF XY:

0.0796

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 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

African (AFR)

AF:

0.0124

AC:

414

AN:

33336

American (AMR)

AF:

0.108

AC:

4705

AN:

43624

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3076

AN:

25820

East Asian (EAS)

AF:

0.000204

AC:

AN:

39148

South Asian (SAS)

AF:

0.0998

AC:

8505

AN:

85202

European-Finnish (FIN)

AF:

0.0645

AC:

3428

AN:

53180

Middle Eastern (MID)

AF:

0.104

AC:

599

AN:

5748

European-Non Finnish (NFE)

AF:

0.0814

AC:

90136

AN:

1107460

Other (OTH)

AF:

0.0787

AC:

4724

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6085

12171

18256

24342

30427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3282

6564

9846

13128

16410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0628

AC:

9560

AN:

152180

Hom.:

381

Cov.:

AF XY:

0.0635

AC XY:

4721

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0150

AC:

623

AN:

41534

American (AMR)

AF:

0.0954

AC:

1459

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

441

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5172

South Asian (SAS)

AF:

0.0857

AC:

413

AN:

4818

European-Finnish (FIN)

AF:

0.0631

AC:

669

AN:

10602

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0839

AC:

5704

AN:

67974

Other (OTH)

AF:

0.0833

AC:

176

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

463

927

1390

1854

2317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0754

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

Jul 13, 2012

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

DANN

Benign

0.92

PhyloP100

0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over