rs1736212

Variant names:

• chr17-17231694-G-C
• rs1736212
• NM_144997.7:c.-25+100C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-17231694-G-C
• chr17-17231694-G-A
• chr17-17231694-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144997.7(FLCN):​c.-25+100C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,324 control chromosomes in the GnomAD database, including 41,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41059 hom., cov: 35)
  • Exomes 𝑓: 0.71 (17 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 5 publications found

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

ENSG00000264187 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 17-17231694-G-C is Benign according to our data. Variant chr17-17231694-G-C is described in ClinVar as Benign. ClinVar VariationId is 1251006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	NM_144997.7	MANE Select	c.-25+100C>G		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.-25+100C>G		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.-308+100C>G		intron	N/A	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	ENST00000285071.9	TSL:1 MANE Select	c.-25+100C>G		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	FLCN	ENST00000389169.9	TSL:1	c.-25+100C>G		intron	N/A	ENSP00000373821.5	Q8NFG4-2
	ENSG00000264187	ENST00000427497.3	TSL:1	n.-25+100C>G		intron	N/A	ENSP00000394249.3	J3QW42

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111134 AN: 152134 Hom.: 41051 Cov.: 35

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.708 AC: 51 AN: 72 Hom.: 17 Cov.: 0 AF XY: 0.740 AC XY: 37 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.889 AC: 16 AN: 18

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.659 AC: 29 AN: 44

Other (OTH) AF: 0.750 AC: 6 AN: 8

GnomAD4 genome AF: 0.730 AC: 111185 AN: 152252 Hom.: 41059 Cov.: 35 AF XY: 0.736 AC XY: 54761 AN XY: 74438

African (AFR) AF: 0.639 AC: 26519 AN: 41530

American (AMR) AF: 0.737 AC: 11280 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2551 AN: 3470

East Asian (EAS) AF: 0.844 AC: 4372 AN: 5178

South Asian (SAS) AF: 0.727 AC: 3515 AN: 4834

European-Finnish (FIN) AF: 0.873 AC: 9269 AN: 10616

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

European-Non Finnish (NFE) AF: 0.753 AC: 51209 AN: 68008

Other (OTH) AF: 0.712 AC: 1505 AN: 2114

Alfa AF: 0.747 Hom.: 5274

Bravo AF: 0.720

Asia WGS AF: 0.780 AC: 2711 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.30
DANN	Benign	0.49
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1736212; hg19: chr17-17135008;