Variant rs2292527 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.619-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 1,600,496 control chromosomes in the GnomAD database, including 2,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 198 hom., cov: 32)

Exomes 𝑓: 0.046 ( 2576 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.46

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=-0.97).

BP6

Variant 17-17222727-G-A is Benign according to our data. Variant chr17-17222727-G-A is described in ClinVar as [Benign]. Clinvar id is 1245008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17222727-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 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.619-66C>T		intron_variant		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.619-66C>T	intron_variant		1	NM_144997.7	ENSP00000285071	P1	Q8NFG4-1
FLCN	ENST00000389169.9 linkuse as main transcript	c.619-66C>T	intron_variant		1		ENSP00000373821		Q8NFG4-2
FLCN	ENST00000466317.1 linkuse as main transcript	n.396C>T	non_coding_transcript_exon_variant	1/2	2
FLCN	ENST00000480316.1 linkuse as main transcript	n.585-66C>T	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5862

AN:

152082

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0350

Gnomad OTH

AF:

0.0316

GnomAD4 exome

AF:

0.0461

AC:

66809

AN:

1448296

Hom.:

2576

Cov.:

AF XY:

0.0493

AC XY:

35552

AN XY:

720920

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0365

Gnomad4 OTH exome

AF:

0.0469

GnomAD4 genome

AF:

0.0386

AC:

5875

AN:

152200

Hom.:

198

Cov.:

AF XY:

0.0404

AC XY:

3007

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0395

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.0263

Gnomad4 NFE

AF:

0.0350

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.22

DANN

Benign

0.40

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