Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000285071.9(FLCN):c.726A>T(p.Thr242Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,614,218 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 97 hom., cov: 32)

Exomes 𝑓: 0.022 ( 434 hom. )

Consequence

FLCN
ENST00000285071.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:20

Conservation

PhyloP100: -8.62

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-17222554-T-A is Benign according to our data. Variant chr17-17222554-T-A is described in ClinVar as Benign. ClinVar VariationId is 96489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000285071.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FLCN	NM_144997.7	MANE Select	c.726A>T	p.Thr242Thr	synonymous	Exon 7 of 14	NP_659434.2
FLCN	NM_001353229.2		c.780A>T	p.Thr260Thr	synonymous	Exon 9 of 16	NP_001340158.1
FLCN	NM_001353230.2		c.726A>T	p.Thr242Thr	synonymous	Exon 8 of 15	NP_001340159.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FLCN	ENST00000285071.9	TSL:1 MANE Select	c.726A>T	p.Thr242Thr	synonymous	Exon 7 of 14	ENSP00000285071.4
FLCN	ENST00000389169.9	TSL:1	c.726A>T	p.Thr242Thr	synonymous	Exon 7 of 8	ENSP00000373821.5
ENSG00000264187	ENST00000427497.3	TSL:1	n.149-3500A>T		intron	N/A	ENSP00000394249.3

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4302

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0196

AC:

4919

AN:

251398

AF XY:

0.0193

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.00919

Gnomad ASJ exome

AF:

0.0304

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.0212

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0220

AC:

32188

AN:

1461888

Hom.:

434

Cov.:

AF XY:

0.0218

AC XY:

15850

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0562

AC:

1882

AN:

33480

American (AMR)

AF:

0.00977

AC:

437

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

764

AN:

26136

East Asian (EAS)

AF:

0.00806

AC:

320

AN:

39700

South Asian (SAS)

AF:

0.0224

AC:

1928

AN:

86258

European-Finnish (FIN)

AF:

0.00425

AC:

227

AN:

53418

Middle Eastern (MID)

AF:

0.0316

AC:

182

AN:

5768

European-Non Finnish (NFE)

AF:

0.0225

AC:

25038

AN:

1112008

Other (OTH)

AF:

0.0233

AC:

1410

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2096

4193

6289

8386

10482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

978

1956

2934

3912

4890

<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:

0.0283

AC:

4305

AN:

152330

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2042

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0547

AC:

2273

AN:

41570

American (AMR)

AF:

0.0144

AC:

220

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

106

AN:

3470

East Asian (EAS)

AF:

0.00347

AC:

AN:

5180

South Asian (SAS)

AF:

0.0190

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0221

AC:

1504

AN:

68034

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

213

427

640

854

1067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0170

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0225

EpiControl

AF:

0.0224

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

not provided (5)

Birt-Hogg-Dube syndrome (3)

Birt-Hogg-Dube syndrome 1 (2)

Familial spontaneous pneumothorax (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

(source)

DANN

Benign

0.86

PhyloP100

-8.6

Mutation Taster

=98/2

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.

rs113938514

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over