Variant 17-17213230-C-T 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.*425G>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 0.0494 in 392,042 control chromosomes in the GnomAD database, including 2,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 2141 hom., cov: 32)

Exomes 𝑓: 0.021 ( 494 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.373

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:

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=-0.88).

BP6

Variant 17-17213230-C-T is Benign according to our data. Variant chr17-17213230-C-T is described in ClinVar as [Benign]. Clinvar id is 322052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7 link	c.*425G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FLCN	ENST00000285071 link	c.*425G>A	3_prime_UTR_variant	Exon 14 of 14	1	NM_144997.7	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3 link	n.*372+1755G>A	intron_variant	Intron 9 of 11	1		ENSP00000394249.3	J3QW42
MPRIP	ENST00000578209.5 link	c.*18-4260C>T	intron_variant	Intron 5 of 5	3		ENSP00000464276.1	J3QRL2

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14232

AN:

152080

Hom.:

2138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0566

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.0693

GnomAD4 exome

AF:

0.0213

AC:

5117

AN:

239844

Hom.:

494

Cov.:

AF XY:

0.0224

AC XY:

2739

AN XY:

122128

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.000111

Gnomad4 EAS exome

AF:

0.0000541

Gnomad4 SAS exome

AF:

0.0527

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.0282

GnomAD4 genome

AF:

0.0936

AC:

14248

AN:

152198

Hom.:

2141

Cov.:

AF XY:

0.0915

AC XY:

6804

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.0352

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0562

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.0686

Alfa

AF:

0.0204

Hom.:

359

Bravo

AF:

0.106

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial spontaneous pneumothorax

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.4

DANN

Benign

0.71

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