chr17-17226304-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBP6BS2
The NM_144997.7(FLCN):c.268G>T(p.Ala90Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000356 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144997.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.268G>T | p.Ala90Ser | missense_variant | Exon 5 of 14 | 1 | NM_144997.7 | ENSP00000285071.4 | ||
ENSG00000264187 | ENST00000427497.3 | n.148+1686G>T | intron_variant | Intron 4 of 11 | 1 | ENSP00000394249.3 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000366 AC: 92AN: 251392Hom.: 0 AF XY: 0.000383 AC XY: 52AN XY: 135890
GnomAD4 exome AF: 0.000365 AC: 534AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.000359 AC XY: 261AN XY: 727246
GnomAD4 genome AF: 0.000263 AC: 40AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74318
ClinVar
Submissions by phenotype
not provided Uncertain:4Benign:4
- -
- -
- -
This variant is associated with the following publications: (PMID: 24728327, 26096009, 22703879, 27734835) -
The FLCN c.268G>T; p.Ala90Ser variant (rs141140415), has not been reported in the medical literature in FLCN-related conditions, but is reported in the ClinVar database (Variation ID: 41857). This variant is found in the general population with an overall allele frequency of 0.03% (97/282,776 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.448). Due to limited information, the clinical significance of this variant is uncertain at this time. -
- -
- -
- -
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
- -
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. -
not specified Benign:1Other:1
- -
- -
Familial spontaneous pneumothorax Uncertain: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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at