Genetic Variant FLCN:c.*1179dupT (chr17-17212475-T-TA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_144997.7(FLCN):c.*1179dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.063 ( 600 hom., cov: 19)

Exomes 𝑓: 0.00094 ( 0 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

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]

FLCN links:

ENSG00000264187 (HGNC:):

ENSG00000264187 links:

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]

MPRIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7 link	c.*1179dupT		3_prime_UTR_variant	Exon 14 of 14	ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FLCN	ENST00000285071 link	c.*1179dupT	3_prime_UTR_variant	Exon 14 of 14	1	NM_144997.7	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3 link	n.*372+2509dupT	intron_variant	Intron 9 of 11	1		ENSP00000394249.3	J3QW42
MPRIP	ENST00000578209.5 link	c.*18-4989dupA	intron_variant	Intron 5 of 5	3		ENSP00000464276.1	J3QRL2

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

4742

AN:

74866

Hom.:

600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00198

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0344

Gnomad EAS

AF:

0.00877

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.00218

Gnomad MID

AF:

0.0234

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0635

GnomAD4 exome

AF:

0.000936

AC:

AN:

1068

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

AN XY:

536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

376

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

Gnomad4 NFE exome

AF:

0.00202

AC:

AN:

494

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0634

AC:

4748

AN:

74892

Hom.:

600

Cov.:

AF XY:

0.0628

AC XY:

2156

AN XY:

34308

show subpopulations

Gnomad4 AFR

AF:

0.191

AC:

0.190688

AN:

0.190688

Gnomad4 AMR

AF:

0.0328

AC:

0.0327532

AN:

0.0327532

Gnomad4 ASJ

AF:

0.0344

AC:

0.0344498

AN:

0.0344498

Gnomad4 EAS

AF:

0.00880

AC:

0.00879567

AN:

0.00879567

Gnomad4 SAS

AF:

0.0386

AC:

0.0386082

AN:

0.0386082

Gnomad4 FIN

AF:

0.00218

AC:

0.00217707

AN:

0.00217707

Gnomad4 NFE

AF:

0.0220

AC:

0.022007

AN:

0.022007

Gnomad4 OTH

AF:

0.0649

AC:

0.0649351

AN:

0.0649351

Heterozygous variant carriers

164

328

491

655

819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00259

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spontaneous pneumothorax

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Birt-Hogg-Dube syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over