17-17221333-T-C
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_144606.7(FLCN):c.*46A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,563,416 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).
Frequency
Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 9 hom. )
Consequence
FLCN
NM_144606.7 3_prime_UTR
NM_144606.7 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.58
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 17-17221333-T-C is Benign according to our data. Variant chr17-17221333-T-C is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0018 (274/152242) while in subpopulation NFE AF= 0.00353 (240/68008). AF 95% confidence interval is 0.00316. There are 1 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 274 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.871+204A>G | intron_variant | ENST00000285071.9 | NP_659434.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000389169 | c.*46A>G | 3_prime_UTR_variant | 8/8 | 1 | ENSP00000373821.5 | ||||
FLCN | ENST00000285071.9 | c.871+204A>G | intron_variant | 1 | NM_144997.7 | ENSP00000285071.4 | ||||
ENSG00000264187 | ENST00000427497.3 | n.149-2279A>G | intron_variant | 1 | ENSP00000394249.3 | |||||
FLCN | ENST00000466317.1 | n.918A>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00180 AC: 274AN: 152124Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00162 AC: 279AN: 172538Hom.: 1 AF XY: 0.00145 AC XY: 133AN XY: 92028
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GnomAD4 exome AF: 0.00315 AC: 4441AN: 1411174Hom.: 9 Cov.: 31 AF XY: 0.00303 AC XY: 2115AN XY: 697574
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GnomAD4 genome AF: 0.00180 AC: 274AN: 152242Hom.: 1 Cov.: 32 AF XY: 0.00156 AC XY: 116AN XY: 74426
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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