17-17213098-A-G

Variant summary

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

The NM_144997.7(FLCN):c.*557T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 258,560 control chromosomes in the GnomAD database, including 66,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39164 hom., cov: 30)

Exomes 𝑓: 0.72 ( 27420 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.144

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=-0.88).

BP6

Variant 17-17213098-A-G is Benign according to our data. Variant chr17-17213098-A-G is described in ClinVar as [Benign]. Clinvar id is 322048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 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.*557T>C		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.*557T>C		3_prime_UTR_variant	14/14	1	NM_144997.7	P1	Q8NFG4-1
MPRIP	ENST00000578209.5 linkuse as main transcript	c.*18-4392A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108627

AN:

151904

Hom.:

39156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.850

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.698

GnomAD4 exome

AF:

0.716

AC:

76274

AN:

106538

Hom.:

27420

Cov.:

AF XY:

0.713

AC XY:

36118

AN XY:

50646

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.709

Gnomad4 ASJ exome

AF:

0.682

Gnomad4 EAS exome

AF:

0.698

Gnomad4 SAS exome

AF:

0.677

Gnomad4 FIN exome

AF:

0.815

Gnomad4 NFE exome

AF:

0.729

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.715

AC:

108678

AN:

152022

Hom.:

39164

Cov.:

AF XY:

0.719

AC XY:

53424

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.657

Gnomad4 AMR

AF:

0.699

Gnomad4 ASJ

AF:

0.696

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.854

Gnomad4 NFE

AF:

0.735

Gnomad4 OTH

AF:

0.690

Alfa

AF:

0.727

Hom.:

83243

Bravo

AF:

0.704

Asia WGS

AF:

0.702

AC:

2438

AN:

3478

ClinVar

Significance: 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 13, 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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

This variant is associated with the following publications: (PMID: 28222720) -

Birt-Hogg-Dube syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

1.8

Dann

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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