rs1736209

Variant names:

• chr17-17237171-C-G
• rs1736209
• ENST00000427497.3:n.-487G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-17237171-C-G
• chr17-17237171-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000427497.3(ENSG00000264187):​n.-487G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,062 control chromosomes in the GnomAD database, including 40,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.73 (40717 hom., cov: 31)
  • Exomes 𝑓: 0.80 (19 hom.)
• Consequence: ENSG00000264187 ENST00000427497.3 non_coding_transcript_exon
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.118
• Publications: 9 publications found

Genes affected

ENSG00000264187 (HGNC:):

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: ClinGen, Genomics England PanelApp, 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, Genomics England PanelApp, Ambry Genetics
• renal carcinoma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• colorectal cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-17237171-C-G is Benign according to our data. Variant chr17-17237171-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 322087.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427497.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	NM_144997.7	MANE Select	c.-487G>C		upstream_gene	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.-695G>C		upstream_gene	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.-770G>C		upstream_gene	N/A	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000264187	ENST00000427497.3	TSL:1	n.-487G>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000394249.3	J3QW42
	ENSG00000264187	ENST00000427497.3	TSL:1	n.-487G>C		5_prime_UTR	Exon 1 of 12	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.-487G>C		5_prime_UTR	Exon 1 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110524 AN: 151888 Hom.: 40709 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.804 AC: 45 AN: 56 Hom.: 19 Cov.: 0 AF XY: 0.781 AC XY: 25 AN XY: 32

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.810 AC: 34 AN: 42

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.727 AC: 110573 AN: 152006 Hom.: 40717 Cov.: 31 AF XY: 0.733 AC XY: 54434 AN XY: 74294

African (AFR) AF: 0.628 AC: 26009 AN: 41436

American (AMR) AF: 0.737 AC: 11271 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2553 AN: 3472

East Asian (EAS) AF: 0.846 AC: 4331 AN: 5118

South Asian (SAS) AF: 0.727 AC: 3495 AN: 4810

European-Finnish (FIN) AF: 0.874 AC: 9266 AN: 10604

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51182 AN: 67958

Other (OTH) AF: 0.711 AC: 1503 AN: 2114

Alfa AF: 0.746 Hom.: 5256

Bravo AF: 0.717

Asia WGS AF: 0.779 AC: 2706 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Birt-Hogg-Dube syndrome (1)
-	1	-	Colorectal cancer;C1868193:Familial spontaneous pneumothorax;CN074294:Nonpapillary renal cell carcinoma;CN375946:Birt-Hogg-Dube syndrome 1 (1)
-	-	1	Familial spontaneous pneumothorax (1)
-	-	1	FLCN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.67
PhyloP100		-0.12
PromoterAI		-0.13	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1736209;

hg19: chr17-17140485;