rs3744123

Variant names:

• chr17-17224156-C-T
• rs3744123
• NM_144997.7:c.397-13G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-17224156-C-T
• chr17-17224156-C-A

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.397-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 1,569,198 control chromosomes in the GnomAD database, including 1,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (706 hom., cov: 33)
  • Exomes 𝑓: 0.028 (1114 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: 0.00600
• Publications: 6 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=-0.85).
• BP6: Variant 17-17224156-C-T is Benign according to our data. Variant chr17-17224156-C-T is described in ClinVar as Benign. ClinVar VariationId is 96485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 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.397-13G>A		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.451-13G>A		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.397-13G>A		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.397-13G>A		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	FLCN	ENST00000389169.9	TSL:1	c.397-13G>A		intron	N/A	ENSP00000373821.5	Q8NFG4-2
	ENSG00000264187	ENST00000427497.3	TSL:1	n.148+3834G>A		intron	N/A	ENSP00000394249.3	J3QW42

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10080 AN: 152184 Hom.: 706 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0599

GnomAD2 exomes AF: 0.0328 AC: 5801 AN: 176948 AF XY: 0.0297

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.0260

Gnomad ASJ exome AF: 0.0336

Gnomad EAS exome AF: 0.000447

Gnomad FIN exome AF: 0.00319

Gnomad NFE exome AF: 0.0265

Gnomad OTH exome AF: 0.0325

GnomAD4 exome AF: 0.0282 AC: 39982 AN: 1416896 Hom.: 1114 Cov.: 31 AF XY: 0.0274 AC XY: 19234 AN XY: 700812

African (AFR) AF: 0.189 AC: 6158 AN: 32610

American (AMR) AF: 0.0269 AC: 1006 AN: 37422

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 805 AN: 25354

East Asian (EAS) AF: 0.00847 AC: 318 AN: 37558

South Asian (SAS) AF: 0.0229 AC: 1863 AN: 81324

European-Finnish (FIN) AF: 0.00442 AC: 221 AN: 50036

Middle Eastern (MID) AF: 0.0647 AC: 365 AN: 5640

European-Non Finnish (NFE) AF: 0.0248 AC: 26992 AN: 1088188

Other (OTH) AF: 0.0384 AC: 2254 AN: 58764

GnomAD4 genome AF: 0.0663 AC: 10096 AN: 152302 Hom.: 706 Cov.: 33 AF XY: 0.0642 AC XY: 4783 AN XY: 74482

African (AFR) AF: 0.179 AC: 7421 AN: 41550

American (AMR) AF: 0.0375 AC: 574 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5180

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4828

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10630

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0249 AC: 1695 AN: 68030

Other (OTH) AF: 0.0592 AC: 125 AN: 2110

Alfa AF: 0.0479 Hom.: 73

Bravo AF: 0.0737

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Birt-Hogg-Dube syndrome (3)
-	-	3	not provided (3)
-	-	2	Birt-Hogg-Dube syndrome 1 (2)
-	-	1	Familial spontaneous pneumothorax (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.1
DANN	Benign	0.53
PhyloP100		0.0060
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs3744123; hg19: chr17-17127470;