dbSNP rs1736215: FLCN:c.-24-727C>T (chr17-17228888-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001353230.2(FLCN):c.-290C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,160 control chromosomes in the GnomAD database, including 21,253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21224 hom., cov: 32)

Exomes 𝑓: 0.55 ( 29 hom. )

Consequence

FLCN
NM_001353230.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

Publications

9 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 Gene-Disease associations (from GenCC):

Birt-Hogg-Dube syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
Birt-Hogg-Dube syndrome 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
familial spontaneous pneumothorax
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp
renal carcinoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
colorectal cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

FLCN links:

ENSG00000264187 (HGNC:):

ENSG00000264187 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353230.2. 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.-24-727C>T	intron	N/A	NP_659434.2
FLCN	NM_001353230.2		c.-290C>T	5_prime_UTR	Exon 4 of 15	NP_001340159.1	Q8NFG4-1
FLCN	NM_001353229.2		c.-24-727C>T	intron	N/A	NP_001340158.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	ENST00000285071.9	TSL:1 MANE Select	c.-24-727C>T	intron	N/A	ENSP00000285071.4	Q8NFG4-1
FLCN	ENST00000389169.9	TSL:1	c.-24-727C>T	intron	N/A	ENSP00000373821.5	Q8NFG4-2
ENSG00000264187	ENST00000427497.3	TSL:1	n.-24-727C>T	intron	N/A	ENSP00000394249.3	J3QW42

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78508

AN:

151894

Hom.:

21221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.554

AC:

AN:

148

Hom.:

Cov.:

AF XY:

0.554

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.857

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.491

AC:

AN:

110

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.517

AC:

78527

AN:

152012

Hom.:

21224

Cov.:

AF XY:

0.523

AC XY:

38817

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.370

AC:

15357

AN:

41454

American (AMR)

AF:

0.547

AC:

8354

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1818

AN:

3472

East Asian (EAS)

AF:

0.625

AC:

3220

AN:

5154

South Asian (SAS)

AF:

0.470

AC:

2259

AN:

4804

European-Finnish (FIN)

AF:

0.730

AC:

7733

AN:

10588

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

38039

AN:

67954

Other (OTH)

AF:

0.479

AC:

1010

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1897

3795

5692

7590

9487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.536

Hom.:

2783

Bravo

AF:

0.499

Asia WGS

AF:

0.573

AC:

1989

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.3

(source)

DANN

Benign

0.50

PhyloP100

0.0080

PromoterAI

-0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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