17-17213262-C-T

Variant summary

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

The NM_144997.7(FLCN):c.*393G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 407,362 control chromosomes in the GnomAD database, including 538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 142 hom., cov: 33)

Exomes 𝑓: 0.042 ( 396 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0630

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-17213262-C-T is Benign according to our data. Variant chr17-17213262-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 322053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 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.*393G>A		3_prime_UTR_variant	14/14	ENST00000285071.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLCN	ENST00000285071.9 linkuse as main transcript	c.*393G>A		3_prime_UTR_variant	14/14	1	NM_144997.7	P1	Q8NFG4-1
MPRIP	ENST00000578209.5 linkuse as main transcript	c.*18-4228C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5320

AN:

152172

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0420

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0879

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0325

GnomAD4 exome

AF:

0.0417

AC:

10633

AN:

255072

Hom.:

396

Cov.:

AF XY:

0.0442

AC XY:

5762

AN XY:

130254

show subpopulations

Gnomad4 AFR exome

AF:

0.0379

Gnomad4 AMR exome

AF:

0.0463

Gnomad4 ASJ exome

AF:

0.0377

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.0783

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0249

Gnomad4 OTH exome

AF:

0.0379

GnomAD4 genome

AF:

0.0350

AC:

5323

AN:

152290

Hom.:

142

Cov.:

AF XY:

0.0370

AC XY:

2757

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0372

Gnomad4 AMR

AF:

0.0418

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.0875

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0280

Hom.:

Bravo

AF:

0.0382

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial spontaneous pneumothorax

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Birt-Hogg-Dube syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

1.9

Dann

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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