dbSNP rs41364753: FLCN:c.1176+68G>C (chr17-17217001-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144997.7(FLCN):c.1176+68G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,182,878 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 162 hom., cov: 33)

Exomes 𝑓: 0.023 ( 345 hom. )

Consequence

FLCN
NM_144997.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.871

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-17217001-C-G is Benign according to our data. Variant chr17-17217001-C-G is described in ClinVar as Benign. ClinVar VariationId is 1284984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

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.1176+68G>C	intron	N/A	NP_659434.2
FLCN	NM_001353229.2		c.1230+68G>C	intron	N/A	NP_001340158.1
FLCN	NM_001353230.2		c.1176+68G>C	intron	N/A	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	ENST00000285071.9	TSL:1 MANE Select	c.1176+68G>C	intron	N/A	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3	TSL:1	n.*10+68G>C	intron	N/A	ENSP00000394249.3	J3QW42
FLCN	ENST00000962729.1		c.1281+68G>C	intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes

AF:

0.0353

AC:

5379

AN:

152172

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0783

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0301

GnomAD4 exome

AF:

0.0226

AC:

23278

AN:

1030588

Hom.:

345

Cov.:

AF XY:

0.0222

AC XY:

11765

AN XY:

530880

show subpopulations

African (AFR)

AF:

0.0837

AC:

2098

AN:

25062

American (AMR)

AF:

0.0126

AC:

536

AN:

42452

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

676

AN:

23186

East Asian (EAS)

AF:

0.00832

AC:

312

AN:

37506

South Asian (SAS)

AF:

0.0218

AC:

1661

AN:

76022

European-Finnish (FIN)

AF:

0.00438

AC:

227

AN:

51774

Middle Eastern (MID)

AF:

0.0357

AC:

152

AN:

4262

European-Non Finnish (NFE)

AF:

0.0226

AC:

16385

AN:

724226

Other (OTH)

AF:

0.0267

AC:

1231

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1246

2491

3737

4982

6228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0354

AC:

5386

AN:

152290

Hom.:

162

Cov.:

AF XY:

0.0344

AC XY:

2560

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0782

AC:

3249

AN:

41532

American (AMR)

AF:

0.0199

AC:

304

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

106

AN:

3470

East Asian (EAS)

AF:

0.00348

AC:

AN:

5172

South Asian (SAS)

AF:

0.0188

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0223

AC:

1514

AN:

68036

Other (OTH)

AF:

0.0298

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

256

511

767

1022

1278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0294

Hom.:

Bravo

AF:

0.0378

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.56

PhyloP100

-0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over