chr17-17221501-C-T

Position:

chr17-17221501-C-T

Variant summary

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

The NM_144606.7(FLCN):c.907G>A(p.Gly303Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 1,613,860 control chromosomes in the GnomAD database, including 3,963 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 591 hom., cov: 32)

Exomes 𝑓: 0.058 ( 3372 hom. )

Consequence

FLCN
NM_144606.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -2.73

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:

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 (MetaRNN=0.001381129).

BP6

Variant 17-17221501-C-T is Benign according to our data. Variant chr17-17221501-C-T is described in ClinVar as [Benign]. Clinvar id is 41861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17221501-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 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.871+36G>A		intron_variant		ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FLCN	ENST00000389169.9 linkuse as main transcript	c.907G>A	p.Gly303Arg	missense_variant	8/8	1		ENSP00000373821.5	Q8NFG4-2
FLCN	ENST00000285071.9 linkuse as main transcript	c.871+36G>A		intron_variant		1	NM_144997.7	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3 linkuse as main transcript	n.149-2447G>A		intron_variant		1		ENSP00000394249.3	J3QW42
FLCN	ENST00000466317.1 linkuse as main transcript	n.750G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0737

AC:

11211

AN:

152122

Hom.:

586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0411

Gnomad ASJ

AF:

0.0502

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.0676

GnomAD3 exomes

AF:

0.0690

AC:

17323

AN:

250996

Hom.:

995

AF XY:

0.0712

AC XY:

9664

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0322

Gnomad ASJ exome

AF:

0.0507

Gnomad EAS exome

AF:

0.194

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0256

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0576

AC:

84152

AN:

1461620

Hom.:

3372

Cov.:

AF XY:

0.0595

AC XY:

43277

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0341

Gnomad4 ASJ exome

AF:

0.0525

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0687

GnomAD4 genome

AF:

0.0738

AC:

11235

AN:

152240

Hom.:

591

Cov.:

AF XY:

0.0742

AC XY:

5523

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0410

Gnomad4 ASJ

AF:

0.0502

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0239

Gnomad4 NFE

AF:

0.0465

Gnomad4 OTH

AF:

0.0707

Alfa

AF:

0.0538

Hom.:

758

Bravo

AF:

0.0791

TwinsUK

AF:

0.0502

AC:

186

ALSPAC

AF:

0.0472

AC:

182

ESP6500AA

AF:

0.131

AC:

579

ESP6500EA

AF:

0.0499

AC:

429

ExAC

AF:

0.0722

AC:

8763

Asia WGS

AF:

0.132

AC:

460

AN:

3478

EpiCase

AF:

0.0521

EpiControl

AF:

0.0472

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jul 13, 2012	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 27120335, 24728327) -

Birt-Hogg-Dube syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Gly303Arg in exon 8A of FLCN: This variant is not expected to have clinical sign ificance because it has been identified in 13.1% (579/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs3744124). -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.20

DANN

Benign

0.64

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.60

REVEL

Benign

0.23

Sift

Benign

0.38

Sift4G

Benign

0.56

Polyphen

0.0020

Vest4

0.083

MutPred

0.25

Gain of MoRF binding (P = 0.0251);

ClinPred

0.00059

GERP RS

-4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

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