dbSNP rs543608114: FLCN:c.*1101C>G (chr17-17212554-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_144997.7(FLCN):c.*1101C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 151,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.881

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS2

High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144997.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	NM_144997.7	MANE Select	c.*1101C>G	3_prime_UTR	Exon 14 of 14	NP_659434.2
FLCN	NM_001353229.2		c.*1101C>G	3_prime_UTR	Exon 16 of 16	NP_001340158.1
FLCN	NM_001353230.2		c.*1101C>G	3_prime_UTR	Exon 15 of 15	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	ENST00000285071.9	TSL:1 MANE Select	c.*1101C>G	3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2431C>G	intron	N/A	ENSP00000394249.3	J3QW42
FLCN	ENST00000962729.1		c.*1101C>G	3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes

AF:

0.0000923

AC:

AN:

151618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000195

AC:

AN:

20542

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

9500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

636

American (AMR)

AF:

0.00

AC:

AN:

442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1316

East Asian (EAS)

AF:

0.00

AC:

AN:

4340

South Asian (SAS)

AF:

0.00

AC:

AN:

174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.000253

AC:

AN:

11872

Other (OTH)

AF:

0.00

AC:

AN:

1628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000923

AC:

AN:

151618

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41250

American (AMR)

AF:

0.000131

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67940

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000170

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Birt-Hogg-Dube syndrome (1)

Familial spontaneous pneumothorax (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.82

PhyloP100

-0.88

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over