rs374707789
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_Very_StrongBP7BS2_Supporting
The NM_144997.7(FLCN):c.1287C>T(p.His429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H429P?) has been classified as Pathogenic.
Frequency
Consequence
NM_144997.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.1287C>T | p.His429= | synonymous_variant | 11/14 | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.1287C>T | p.His429= | synonymous_variant | 11/14 | 1 | NM_144997.7 | P1 | |
MPRIP | ENST00000578209.5 | c.*18-1097G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000363 AC: 9AN: 248098Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134588
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461192Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 726918
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
FLCN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 04, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 24, 2017 | 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:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at