17-17216890-T-C

Variant names:

• chr17-17216890-T-C
• rs7208065
• NM_144997.7:c.1176+179A>G

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.1176+179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 662,790 control chromosomes in the GnomAD database, including 98,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20840 hom., cov: 33)
  • Exomes 𝑓: 0.55 (77551 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.123
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-17216890-T-C is Benign according to our data. Variant chr17-17216890-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 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.1176+179A>G		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1230+179A>G		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1176+179A>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.1176+179A>G		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*10+179A>G		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.1281+179A>G		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77904 AN: 151970 Hom.: 20835 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.546 AC: 278799 AN: 510702 Hom.: 77551 AF XY: 0.541 AC XY: 147416 AN XY: 272616

African (AFR) AF: 0.372 AC: 5492 AN: 14752

American (AMR) AF: 0.571 AC: 17436 AN: 30524

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 8489 AN: 17428

East Asian (EAS) AF: 0.650 AC: 20435 AN: 31448

South Asian (SAS) AF: 0.473 AC: 26745 AN: 56490

European-Finnish (FIN) AF: 0.700 AC: 22775 AN: 32546

Middle Eastern (MID) AF: 0.408 AC: 918 AN: 2250

European-Non Finnish (NFE) AF: 0.544 AC: 161508 AN: 296768

Other (OTH) AF: 0.526 AC: 15001 AN: 28496

GnomAD4 genome AF: 0.512 AC: 77932 AN: 152088 Hom.: 20840 Cov.: 33 AF XY: 0.519 AC XY: 38619 AN XY: 74354

African (AFR) AF: 0.379 AC: 15730 AN: 41486

American (AMR) AF: 0.532 AC: 8130 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3428 AN: 5164

South Asian (SAS) AF: 0.485 AC: 2338 AN: 4824

European-Finnish (FIN) AF: 0.729 AC: 7724 AN: 10592

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37156 AN: 67952

Other (OTH) AF: 0.471 AC: 996 AN: 2114

Alfa AF: 0.530 Hom.: 3442

Bravo AF: 0.495

Asia WGS AF: 0.595 AC: 2065 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.90
CADD	Benign	0.95
DANN	Benign	0.66
PhyloP100		-0.12
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)		0.0		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: rs7208065; hg19: chr17-17120204;