rs4985751
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_144997.7(FLCN):c.1063-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00913 in 765,972 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0089 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0092 ( 80 hom. )
Consequence
FLCN
NM_144997.7 intron
NM_144997.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.982
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 17-17217299-G-A is Benign according to our data. Variant chr17-17217299-G-A is described in ClinVar as [Benign]. Clinvar id is 1238435.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-17217299-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00894 (1362/152336) while in subpopulation AMR AF= 0.0349 (534/15302). AF 95% confidence interval is 0.0325. There are 18 homozygotes in gnomad4. There are 647 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1362 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.1063-117C>T | intron_variant | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.1063-117C>T | intron_variant | 1 | NM_144997.7 | P1 | |||
MPRIP | ENST00000578209.5 | c.*18-191G>A | intron_variant | 3 | |||||
FLCN | ENST00000577591.1 | n.86-117C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00892 AC: 1358AN: 152218Hom.: 18 Cov.: 33
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GnomAD4 exome AF: 0.00918 AC: 5635AN: 613636Hom.: 80 AF XY: 0.00832 AC XY: 2731AN XY: 328244
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GnomAD4 genome ? AF: 0.00894 AC: 1362AN: 152336Hom.: 18 Cov.: 33 AF XY: 0.00869 AC XY: 647AN XY: 74496
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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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