rs41364753

Positions:

• chr17-17217001-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144997.7(FLCN):​c.1176+68G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,182,878 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (162 hom., cov: 33)
  • Exomes 𝑓: 0.023 (345 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.871

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]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-17217001-C-G is Benign according to our data. Variant chr17-17217001-C-G is described in ClinVar as [Benign]. Clinvar id is 1284984.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-17217001-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLCN	NM_144997.7	c.1176+68G>C		intron_variant		ENST00000285071.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLCN	ENST00000285071.9	c.1176+68G>C		intron_variant		1	NM_144997.7	P1
MPRIP	ENST00000578209.5	c.*18-489C>G		intron_variant		3
FLCN	ENST00000577591.1	n.267G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5379 AN: 152172 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0226 AC: 23278 AN: 1030588 Hom.: 345 Cov.: 14 AF XY: 0.0222 AC XY: 11765 AN XY: 530880

Gnomad4 AFR exome AF: 0.0837

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0292

Gnomad4 EAS exome AF: 0.00832

Gnomad4 SAS exome AF: 0.0218

Gnomad4 FIN exome AF: 0.00438

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0267

GnomAD4 genome AF: 0.0354 AC: 5386 AN: 152290 Hom.: 162 Cov.: 33 AF XY: 0.0344 AC XY: 2560 AN XY: 74478

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0294 Hom.: 11

Bravo AF: 0.0378

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs41364753; hg19: chr17-17120315;