rs878855217
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001353229.2(FLCN):c.638delG(p.Gly213GlufsTer28) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
FLCN
NM_001353229.2 frameshift
NM_001353229.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.93
Publications
3 publications found
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 syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
- Birt-Hogg-Dube syndrome 1Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
- familial spontaneous pneumothoraxInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics
- renal carcinomaInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- colorectal cancerInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-17223955-TC-T is Pathogenic according to our data. Variant chr17-17223955-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 241927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001353229.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FLCN | NM_144997.7 | MANE Select | c.584delG | p.Gly195GlufsTer28 | frameshift | Exon 6 of 14 | NP_659434.2 | ||
| FLCN | NM_001353229.2 | c.638delG | p.Gly213GlufsTer28 | frameshift | Exon 8 of 16 | NP_001340158.1 | |||
| FLCN | NM_001353230.2 | c.584delG | p.Gly195GlufsTer28 | frameshift | Exon 7 of 15 | NP_001340159.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FLCN | ENST00000285071.9 | TSL:1 MANE Select | c.584delG | p.Gly195GlufsTer28 | frameshift | Exon 6 of 14 | ENSP00000285071.4 | ||
| FLCN | ENST00000389169.9 | TSL:1 | c.584delG | p.Gly195GlufsTer28 | frameshift | Exon 6 of 8 | ENSP00000373821.5 | ||
| ENSG00000264187 | ENST00000427497.3 | TSL:1 | n.148+4034delG | intron | N/A | ENSP00000394249.3 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152216
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152216
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74364
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41448
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68050
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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Age
Alfa
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ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Birt-Hogg-Dube syndrome (4)
1
-
-
Birt-Hogg-Dube syndrome 1 (1)
1
-
-
FLCN-related disorder (1)
1
-
-
Hereditary cancer-predisposing syndrome (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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