rs201810397
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_144997.7(FLCN):c.1692C>T(p.His564=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,614,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 1 hom. )
Consequence
FLCN
NM_144997.7 synonymous
NM_144997.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.28
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]
MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 17-17213703-G-A is Benign according to our data. Variant chr17-17213703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 184907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.28 with no splicing effect.
BS2
?
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.1692C>T | p.His564= | synonymous_variant | 14/14 | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.1692C>T | p.His564= | synonymous_variant | 14/14 | 1 | NM_144997.7 | P1 | |
MPRIP | ENST00000578209.5 | c.*18-3787G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000954 AC: 24AN: 251488Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135918
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GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461888Hom.: 1 Cov.: 31 AF XY: 0.0000784 AC XY: 57AN XY: 727244
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 21, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 05, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 21, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Birt-Hogg-Dube syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Birt-Hogg-Dube syndrome;C0346629:Colorectal cancer;C1868193:Familial spontaneous pneumothorax;C2931246:Potocki-Lupski syndrome;CN074294:Nonpapillary renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 12, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at