Variant 17-17217354-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_144997.7(FLCN):c.1063-172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 656,626 control chromosomes in the GnomAD database, including 98,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.51 ( 20889 hom., cov: 33)

Exomes 𝑓: 0.55 ( 77141 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.16

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:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-17217354-G-C is Benign according to our data. Variant chr17-17217354-G-C is described in ClinVar as [Benign]. Clinvar id is 1232218.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-17217354-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLCN	NM_144997.7 linkuse as main transcript	c.1063-172C>G		intron_variant		ENST00000285071.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
FLCN	ENST00000285071.9 linkuse as main transcript	c.1063-172C>G	intron_variant	1	NM_144997.7	P1	Q8NFG4-1
MPRIP	ENST00000578209.5 linkuse as main transcript	c.*18-136G>C	intron_variant	3
FLCN	ENST00000577591.1 linkuse as main transcript	n.86-172C>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77949

AN:

151994

Hom.:

20885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.476

GnomAD4 exome

AF:

0.548

AC:

276673

AN:

504514

Hom.:

77141

AF XY:

0.543

AC XY:

146793

AN XY:

270284

show subpopulations

Gnomad4 AFR exome

AF:

0.369

Gnomad4 AMR exome

AF:

0.575

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.471

Gnomad4 FIN exome

AF:

0.700

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.513

AC:

77972

AN:

152112

Hom.:

20889

Cov.:

AF XY:

0.519

AC XY:

38584

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.491

Gnomad4 EAS

AF:

0.663

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.729

Gnomad4 NFE

AF:

0.550

Gnomad4 OTH

AF:

0.471

Alfa

AF:

0.408

Hom.:

1238

Bravo

AF:

0.495

Asia WGS

AF:

0.593

AC:

2060

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.058

DANN

Benign

0.54

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