rs1736219

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144997.7(FLCN):c.397-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,566,246 control chromosomes in the GnomAD database, including 181,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 15061 hom., cov: 33)

Exomes 𝑓: 0.48 ( 166459 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: -0.00600

Publications

22 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, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
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: Orphanet, Ambry Genetics, Genomics England PanelApp
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-17224157-G-A is Benign according to our data. Variant chr17-17224157-G-A is described in ClinVar as Benign. ClinVar VariationId is 96486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144997.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	NM_144997.7	MANE Select	c.397-14C>T	intron	N/A	NP_659434.2
FLCN	NM_001353229.2		c.451-14C>T	intron	N/A	NP_001340158.1
FLCN	NM_001353230.2		c.397-14C>T	intron	N/A	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	ENST00000285071.9	TSL:1 MANE Select	c.397-14C>T	intron	N/A	ENSP00000285071.4	Q8NFG4-1
FLCN	ENST00000389169.9	TSL:1	c.397-14C>T	intron	N/A	ENSP00000373821.5	Q8NFG4-2
ENSG00000264187	ENST00000427497.3	TSL:1	n.148+3833C>T	intron	N/A	ENSP00000394249.3	J3QW42

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61935

AN:

152008

Hom.:

15063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.396

GnomAD2 exomes

AF:

0.482

AC:

84710

AN:

175706

AF XY:

0.474

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.658

Gnomad FIN exome

AF:

0.661

Gnomad NFE exome

AF:

0.487

Gnomad OTH exome

AF:

0.457

GnomAD4 exome

AF:

0.478

AC:

676428

AN:

1414120

Hom.:

166459

Cov.:

AF XY:

0.475

AC XY:

332177

AN XY:

699100

show subpopulations

African (AFR)

AF:

0.136

AC:

4413

AN:

32518

American (AMR)

AF:

0.530

AC:

19673

AN:

37100

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

10522

AN:

25342

East Asian (EAS)

AF:

0.648

AC:

24258

AN:

37432

South Asian (SAS)

AF:

0.353

AC:

28603

AN:

81044

European-Finnish (FIN)

AF:

0.644

AC:

32087

AN:

49818

Middle Eastern (MID)

AF:

0.330

AC:

1851

AN:

5612

European-Non Finnish (NFE)

AF:

0.486

AC:

528471

AN:

1086606

Other (OTH)

AF:

0.453

AC:

26550

AN:

58648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

17137

34274

51411

68548

85685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15590

31180

46770

62360

77950

<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:

0.407

AC:

61943

AN:

152126

Hom.:

15061

Cov.:

AF XY:

0.415

AC XY:

30842

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.150

AC:

6228

AN:

41544

American (AMR)

AF:

0.469

AC:

7168

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1467

AN:

3472

East Asian (EAS)

AF:

0.663

AC:

3417

AN:

5154

South Asian (SAS)

AF:

0.368

AC:

1774

AN:

4824

European-Finnish (FIN)

AF:

0.668

AC:

7068

AN:

10578

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33288

AN:

67954

Other (OTH)

AF:

0.392

AC:

829

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1704

3408

5113

6817

8521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.428

Hom.:

23942

Bravo

AF:

0.385

Asia WGS

AF:

0.521

AC:

1809

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Birt-Hogg-Dube syndrome (4)

not provided (3)

Familial spontaneous pneumothorax (2)

Birt-Hogg-Dube syndrome 1 (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.71

(source)

DANN

Benign

0.57

PhyloP100

-0.0060

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over