Variant 17-17212741-G-A 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.*914C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 191,454 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.043 ( 251 hom., cov: 31)

Exomes 𝑓: 0.029 ( 13 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.04

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 17-17212741-G-A is Benign according to our data. Variant chr17-17212741-G-A is described in ClinVar as [Benign]. Clinvar id is 322041.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7 link	c.*914C>T		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.*914C>T	3_prime_UTR_variant	Exon 14 of 14	1	NM_144997.7	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3 link	n.*372+2244C>T	intron_variant	Intron 9 of 11	1		ENSP00000394249.3	J3QW42
MPRIP	ENST00000578209.5 link	c.*18-4749G>A	intron_variant	Intron 5 of 5	3		ENSP00000464276.1	J3QRL2

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6536

AN:

151892

Hom.:

248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0953

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0295

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.00483

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0388

GnomAD4 exome

AF:

0.0287

AC:

1131

AN:

39444

Hom.:

Cov.:

AF XY:

0.0282

AC XY:

519

AN XY:

18408

show subpopulations

Gnomad4 AFR exome

AF:

0.0847

Gnomad4 AMR exome

AF:

0.0289

Gnomad4 ASJ exome

AF:

0.0341

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0283

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0431

AC:

6559

AN:

152010

Hom.:

251

Cov.:

AF XY:

0.0425

AC XY:

3156

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0956

Gnomad4 AMR

AF:

0.0295

Gnomad4 ASJ

AF:

0.0378

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.00483

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0384

Alfa

AF:

0.0363

Hom.:

Bravo

AF:

0.0479

Asia WGS

AF:

0.0300

AC:

103

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial spontaneous pneumothorax

Benign:1

Jan 13, 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 13, 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

-1.0

CADD

Benign

0.80

DANN

Benign

0.15

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