rs1708629
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_144997.7(FLCN):c.-299C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,880 control chromosomes in the GnomAD database, including 18,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.45 ( 18612 hom., cov: 31)
Exomes 𝑓: 0.58 ( 8 hom. )
Consequence
FLCN
NM_144997.7 5_prime_UTR
NM_144997.7 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.728
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 17-17236983-G-A is Benign according to our data. Variant chr17-17236983-G-A is described in ClinVar as [Benign]. Clinvar id is 322082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17236983-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.-299C>T | 5_prime_UTR_variant | 1/14 | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.-299C>T | 5_prime_UTR_variant | 1/14 | 1 | NM_144997.7 | P1 | ||
FLCN | ENST00000389169.9 | c.-299C>T | 5_prime_UTR_variant | 1/8 | 1 | ||||
FLCN | ENST00000417064.1 | c.-99C>T | 5_prime_UTR_variant | 1/4 | 2 | ||||
FLCN | ENST00000389171.4 | n.206C>T | non_coding_transcript_exon_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.453 AC: 68687AN: 151714Hom.: 18617 Cov.: 31
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GnomAD4 exome AF: 0.583 AC: 28AN: 48Hom.: 8 Cov.: 0 AF XY: 0.533 AC XY: 16AN XY: 30
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GnomAD4 genome ? AF: 0.452 AC: 68681AN: 151832Hom.: 18612 Cov.: 31 AF XY: 0.460 AC XY: 34108AN XY: 74170
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial spontaneous pneumothorax Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | - - |
Birt-Hogg-Dube syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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