Variant rs1708629 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.-299C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,880 control chromosomes in the GnomAD database, including 18,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 18612 hom., cov: 31)

Exomes 𝑓: 0.58 ( 8 hom. )

Consequence

FLCN
NM_144997.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.728

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-17236983-G-A is Benign according to our data. Variant chr17-17236983-G-A is described in ClinVar as [Benign]. Clinvar id is 322082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17236983-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 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.-299C>T		5_prime_UTR_variant	1/14	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9 linkuse as main transcript	c.-299C>T	5_prime_UTR_variant	1/14	1	NM_144997.7	ENSP00000285071	P1	Q8NFG4-1
FLCN	ENST00000389169.9 linkuse as main transcript	c.-299C>T	5_prime_UTR_variant	1/8	1		ENSP00000373821		Q8NFG4-2
FLCN	ENST00000417064.1 linkuse as main transcript	c.-99C>T	5_prime_UTR_variant	1/4	2		ENSP00000410410
FLCN	ENST00000389171.4 linkuse as main transcript	n.206C>T	non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68687

AN:

151714

Hom.:

18617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.583

AC:

AN:

Hom.:

Cov.:

AF XY:

0.533

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.452

AC:

68681

AN:

151832

Hom.:

18612

Cov.:

AF XY:

0.460

AC XY:

34108

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.527

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.732

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.494

Hom.:

2511

Bravo

AF:

0.427

Asia WGS

AF:

0.529

AC:

1835

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	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

FLCN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial spontaneous pneumothorax

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Birt-Hogg-Dube syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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