Variant chr17-17217038-C-T 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.1176+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,502,228 control chromosomes in the GnomAD database, including 438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 42 hom., cov: 33)

Exomes 𝑓: 0.019 ( 396 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.123

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

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-17217038-C-T is Benign according to our data. Variant chr17-17217038-C-T is described in ClinVar as [Benign]. Clinvar id is 496848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17217038-C-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7 linkuse as main transcript	c.1176+31G>A		intron_variant		ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FLCN	ENST00000285071.9 linkuse as main transcript	c.1176+31G>A	intron_variant		1	NM_144997.7	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3 linkuse as main transcript	n.*10+31G>A	intron_variant		1		ENSP00000394249.3	J3QW42
MPRIP	ENST00000578209.5 linkuse as main transcript	c.*18-452C>T	intron_variant		3		ENSP00000464276.1	J3QRL2
FLCN	ENST00000577591.1 linkuse as main transcript	n.230G>A	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2398

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0432

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0247

AC:

6161

AN:

249196

Hom.:

132

AF XY:

0.0251

AC XY:

3384

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.00315

Gnomad AMR exome

AF:

0.0646

Gnomad ASJ exome

AF:

0.0158

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0446

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0195

GnomAD4 exome

AF:

0.0193

AC:

26112

AN:

1349952

Hom.:

396

Cov.:

AF XY:

0.0200

AC XY:

13555

AN XY:

677822

show subpopulations

Gnomad4 AFR exome

AF:

0.00247

Gnomad4 AMR exome

AF:

0.0623

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0445

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0174

Gnomad4 OTH exome

AF:

0.0156

GnomAD4 genome

AF:

0.0157

AC:

2397

AN:

152276

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1231

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.0379

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0432

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 09, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.7

DANN

Benign

0.53

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