17-17212472-C-CT

Position:

• chr17-17212472-C-CT

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7	c.*1182dupA		3_prime_UTR_variant	14/14	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071	c.*1182dupA		3_prime_UTR_variant	14/14	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.*372+2512dupA		intron_variant		1		ENSP00000394249.3
MPRIP	ENST00000578209.5	c.*18-5015dupT		intron_variant		3		ENSP00000464276.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00980

Gnomad4 EAS exome AF: 0.00948

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00340

Gnomad4 OTH exome AF: 0.00980

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

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.0547

Gnomad4 ASJ AF: 0.0339

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0264

Gnomad4 OTH AF: 0.0519

Alfa AF: 0.00478 Hom.: 0

Asia WGS AF: 0.0250 AC: 84 AN: 3436

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Spontaneous pneumothorax Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Birt-Hogg-Dube syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs199535675; hg19: chr17-17115786;