NM_144997.7:c.1063-172C>G

Variant names:

• chr17-17217354-G-C
• rs4985705
• NM_144997.7:c.1063-172C>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.1063-172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 656,626 control chromosomes in the GnomAD database, including 98,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20889 hom., cov: 33)
  • Exomes 𝑓: 0.55 (77141 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.16
• Publications: 10 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=-0.91).
• BP6: Variant 17-17217354-G-C is Benign according to our data. Variant chr17-17217354-G-C is described in ClinVar as Benign. ClinVar VariationId is 1232218.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.1063-172C>G		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1117-172C>G		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1063-172C>G		intron	N/A	NP_001340159.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	ENST00000285071.9	TSL:1 MANE Select	c.1063-172C>G		intron	N/A	ENSP00000285071.4
	ENSG00000264187	ENST00000427497.3	TSL:1	n.185-172C>G		intron	N/A	ENSP00000394249.3
	FLCN	ENST00000962729.1		c.1168-172C>G		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77949 AN: 151994 Hom.: 20885 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.548 AC: 276673 AN: 504514 Hom.: 77141 AF XY: 0.543 AC XY: 146793 AN XY: 270284

African (AFR) AF: 0.369 AC: 5211 AN: 14124

American (AMR) AF: 0.575 AC: 16781 AN: 29194

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 8619 AN: 17560

East Asian (EAS) AF: 0.649 AC: 20434 AN: 31478

South Asian (SAS) AF: 0.471 AC: 26275 AN: 55816

European-Finnish (FIN) AF: 0.700 AC: 22240 AN: 31770

Middle Eastern (MID) AF: 0.406 AC: 999 AN: 2460

European-Non Finnish (NFE) AF: 0.548 AC: 161096 AN: 293734

Other (OTH) AF: 0.529 AC: 15018 AN: 28378

GnomAD4 genome AF: 0.513 AC: 77972 AN: 152112 Hom.: 20889 Cov.: 33 AF XY: 0.519 AC XY: 38584 AN XY: 74370

African (AFR) AF: 0.376 AC: 15585 AN: 41490

American (AMR) AF: 0.531 AC: 8113 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1705 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3433 AN: 5176

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4822

European-Finnish (FIN) AF: 0.729 AC: 7721 AN: 10598

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

European-Non Finnish (NFE) AF: 0.550 AC: 37390 AN: 67974

Other (OTH) AF: 0.471 AC: 991 AN: 2106

Alfa AF: 0.408 Hom.: 1238

Bravo AF: 0.495

Asia WGS AF: 0.593 AC: 2060 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	-0.91
CADD	Benign	0.058
DANN	Benign	0.54
PhyloP100		-2.2
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: rs4985705; hg19: chr17-17120668;