rs878855216

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_144997.7(FLCN):c.357C>T(p.Ser119Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,866 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 Likely benign (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FLCN
NM_144997.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.17

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 Gene-Disease associations (from GenCC):

Birt-Hogg-Dube syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
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: Genomics England PanelApp, Orphanet, Ambry Genetics
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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-17226215-G-A is Benign according to our data. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17226215-G-A is described in CliVar as Likely_benign. Clinvar id is 241923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.17 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7 link	c.357C>T	p.Ser119Ser	synonymous_variant	Exon 5 of 14	ENST00000285071.9	NP_659434.2	Q8NFG4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9 link	c.357C>T	p.Ser119Ser	synonymous_variant	Exon 5 of 14	1	NM_144997.7	ENSP00000285071.4		Q8NFG4-1
ENSG00000264187	ENST00000427497.3 link	n.148+1775C>T		intron_variant	Intron 4 of 11	1		ENSP00000394249.3		J3QW42

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:1

Oct 27, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Birt-Hogg-Dube syndrome

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.35

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over