17-17228063-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_144997.7(FLCN):c.75G>A(p.Leu25Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,613,766 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L25L) has been classified as Likely benign.
Frequency
Consequence
NM_144997.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.75G>A | p.Leu25Leu | synonymous_variant | Exon 4 of 14 | 1 | NM_144997.7 | ENSP00000285071.4 | ||
ENSG00000264187 | ENST00000427497.3 | n.75G>A | non_coding_transcript_exon_variant | Exon 4 of 12 | 1 | ENSP00000394249.3 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000570 AC: 143AN: 250934Hom.: 1 AF XY: 0.000685 AC XY: 93AN XY: 135792
GnomAD4 exome AF: 0.000250 AC: 365AN: 1461394Hom.: 3 Cov.: 31 AF XY: 0.000341 AC XY: 248AN XY: 727010
GnomAD4 genome AF: 0.000158 AC: 24AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74526
ClinVar
Submissions by phenotype
not provided Benign:4
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FLCN: BP4, BP7, BS1 -
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Birt-Hogg-Dube syndrome 1 Benign:2
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This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Hereditary cancer-predisposing syndrome Benign:2
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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
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. -
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not specified Benign:1
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Birt-Hogg-Dube syndrome;C0346629:Colorectal cancer;C1868193:Familial spontaneous pneumothorax;C2931246:17p11.2 microduplication syndrome;CN074294:Nonpapillary renal cell carcinoma Benign:1
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Familial spontaneous pneumothorax Benign:1
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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at