Variant 17-17215128-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144997.7(FLCN):c.1433-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,376 control chromosomes in the GnomAD database, including 58,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.22 ( 4034 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54466 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.802

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-17215128-T-C is Benign according to our data. Variant chr17-17215128-T-C is described in ClinVar as [Benign]. Clinvar id is 253253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17215128-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7 link	c.1433-38A>G		intron_variant		ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FLCN	ENST00000285071.9 link	c.1433-38A>G	intron_variant	1	NM_144997.7	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3 link	n.*267-38A>G	intron_variant	1		ENSP00000394249.3	J3QW42
MPRIP	ENST00000578209.5 link	c.*18-2362T>C	intron_variant	3		ENSP00000464276.1	J3QRL2

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32662

AN:

151540

Hom.:

4028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.00296

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.235

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.238

GnomAD3 exomes

AF:

0.233

AC:

58535

AN:

251172

Hom.:

7694

AF XY:

0.237

AC XY:

32110

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.266

AC:

388239

AN:

1461722

Hom.:

54466

Cov.:

AF XY:

0.265

AC XY:

192483

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.216

AC:

32692

AN:

151654

Hom.:

4034

Cov.:

AF XY:

0.217

AC XY:

16048

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.00297

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.284

Gnomad4 NFE

AF:

0.276

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.243

Hom.:

942

Bravo

AF:

0.205

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Birt-Hogg-Dube syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jul 18, 2016	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.98

DANN

Benign

0.40

BranchPoint Hunter

4.0

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