17-17212475-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_144997.7(FLCN):​c.*1179delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0098 ( 7 hom., cov: 19)
Exomes 𝑓: 0.0056 ( 0 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.602
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00979 (734/74958) while in subpopulation AMR AF= 0.0348 (220/6320). AF 95% confidence interval is 0.031. There are 7 homozygotes in gnomad4. There are 325 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.
BS2
High AC in GnomAd4 at 734 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLCNNM_144997.7 linkc.*1179delT 3_prime_UTR_variant Exon 14 of 14 ENST00000285071.9 NP_659434.2 Q8NFG4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLCNENST00000285071 linkc.*1179delT 3_prime_UTR_variant Exon 14 of 14 1 NM_144997.7 ENSP00000285071.4 Q8NFG4-1
ENSG00000264187ENST00000427497.3 linkn.*372+2509delT intron_variant Intron 9 of 11 1 ENSP00000394249.3 J3QW42
MPRIPENST00000578209.5 linkc.*18-4989delA intron_variant Intron 5 of 5 3 ENSP00000464276.1 J3QRL2

Frequencies

GnomAD3 genomes
AF:
0.00980
AC:
734
AN:
74932
Hom.:
7
Cov.:
19
show subpopulations
Gnomad AFR
AF:
0.00661
Gnomad AMI
AF:
0.00198
Gnomad AMR
AF:
0.0349
Gnomad ASJ
AF:
0.00622
Gnomad EAS
AF:
0.0209
Gnomad SAS
AF:
0.00664
Gnomad FIN
AF:
0.00109
Gnomad MID
AF:
0.00781
Gnomad NFE
AF:
0.00743
Gnomad OTH
AF:
0.0109
GnomAD4 exome
AF:
0.00562
AC:
6
AN:
1068
Hom.:
0
Cov.:
0
AF XY:
0.00560
AC XY:
3
AN XY:
536
show subpopulations
Gnomad4 AFR exome
AF:
0.0278
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00532
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00405
Gnomad4 OTH exome
AF:
0.0139
GnomAD4 genome
AF:
0.00979
AC:
734
AN:
74958
Hom.:
7
Cov.:
19
AF XY:
0.00946
AC XY:
325
AN XY:
34340
show subpopulations
Gnomad4 AFR
AF:
0.00659
Gnomad4 AMR
AF:
0.0348
Gnomad4 ASJ
AF:
0.00622
Gnomad4 EAS
AF:
0.0210
Gnomad4 SAS
AF:
0.00666
Gnomad4 FIN
AF:
0.00109
Gnomad4 NFE
AF:
0.00744
Gnomad4 OTH
AF:
0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs397932764; hg19: chr17-17115789; API