rs767345167
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting
The NM_144997.7(FLCN):c.1737C>T(p.Asn579=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,176 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
FLCN
NM_144997.7 synonymous
NM_144997.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.135
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 17-17213658-G-A is Benign according to our data. Variant chr17-17213658-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 530016.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.135 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.1737C>T | p.Asn579= | synonymous_variant | 14/14 | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.1737C>T | p.Asn579= | synonymous_variant | 14/14 | 1 | NM_144997.7 | P1 | |
MPRIP | ENST00000578209.5 | c.*18-3832G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727220
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Birt-Hogg-Dube syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 29, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at