17-17212472-CT-CTT

Variant names:

• chr17-17212472-C-CT
• rs199535675
• NM_144997.7:c.*1182dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144997.7(FLCN):​c.*1182dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (171 hom., cov: 20)
  • Exomes 𝑓: 0.0062 (0 hom.)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.536
• Publications: 0 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]

ENSG00000264187 (HGNC:):

MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-17212472-C-CT is Benign according to our data. Variant chr17-17212472-C-CT is described in ClinVar as Benign. ClinVar VariationId is 322036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 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.*1182dupA		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*1182dupA		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*1182dupA		3_prime_UTR	Exon 15 of 15	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.*1182dupA		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2512dupA		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*1182dupA		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 4269 AN: 85986 Hom.: 168 Cov.: 20

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.00361

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0339

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0662

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0477

GnomAD4 exome AF: 0.00621 AC: 8 AN: 1288 Hom.: 0 Cov.: 0 AF XY: 0.00637 AC XY: 4 AN XY: 628

African (AFR) AF: 0.00 AC: 0 AN: 34

American (AMR) AF: 0.00 AC: 0 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 1 AN: 102

East Asian (EAS) AF: 0.00948 AC: 4 AN: 422

South Asian (SAS) AF: 0.00 AC: 0 AN: 12

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00340 AC: 2 AN: 588

Other (OTH) AF: 0.00980 AC: 1 AN: 102

GnomAD4 genome AF: 0.0497 AC: 4278 AN: 85998 Hom.: 171 Cov.: 20 AF XY: 0.0521 AC XY: 2063 AN XY: 39568

African (AFR) AF: 0.0931 AC: 1892 AN: 20316

American (AMR) AF: 0.0547 AC: 392 AN: 7172

Ashkenazi Jewish (ASJ) AF: 0.0339 AC: 81 AN: 2388

East Asian (EAS) AF: 0.113 AC: 368 AN: 3254

South Asian (SAS) AF: 0.0896 AC: 235 AN: 2624

European-Finnish (FIN) AF: 0.0145 AC: 45 AN: 3096

Middle Eastern (MID) AF: 0.0703 AC: 9 AN: 128

European-Non Finnish (NFE) AF: 0.0264 AC: 1200 AN: 45426

Other (OTH) AF: 0.0519 AC: 54 AN: 1040

Alfa AF: 0.00478 Hom.: 0

Asia WGS AF: 0.0250 AC: 84 AN: 3436

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Birt-Hogg-Dube syndrome (1)
-	-	1	Spontaneous pneumothorax (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
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: rs199535675; hg19: chr17-17115786;