NM_144997.7:c.*393G>A

Variant names:

• chr17-17213262-C-T
• rs12602675
• NM_144997.7:c.*393G>A

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.*393G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 407,362 control chromosomes in the GnomAD database, including 538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (142 hom., cov: 33)
  • Exomes 𝑓: 0.042 (396 hom.)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0630
• Publications: 9 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=-0.87).
• BP6: Variant 17-17213262-C-T is Benign according to our data. Variant chr17-17213262-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 322053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 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.*393G>A		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*393G>A		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*393G>A		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.*393G>A		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+1723G>A		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*393G>A		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5320 AN: 152172 Hom.: 139 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0417 AC: 10633 AN: 255072 Hom.: 396 Cov.: 0 AF XY: 0.0442 AC XY: 5762 AN XY: 130254

African (AFR) AF: 0.0379 AC: 347 AN: 9160

American (AMR) AF: 0.0463 AC: 496 AN: 10722

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 352 AN: 9342

East Asian (EAS) AF: 0.129 AC: 2462 AN: 19058

South Asian (SAS) AF: 0.0783 AC: 2442 AN: 31180

European-Finnish (FIN) AF: 0.0172 AC: 152 AN: 8836

Middle Eastern (MID) AF: 0.0519 AC: 59 AN: 1136

European-Non Finnish (NFE) AF: 0.0249 AC: 3731 AN: 150036

Other (OTH) AF: 0.0379 AC: 592 AN: 15602

GnomAD4 genome AF: 0.0350 AC: 5323 AN: 152290 Hom.: 142 Cov.: 33 AF XY: 0.0370 AC XY: 2757 AN XY: 74466

African (AFR) AF: 0.0372 AC: 1548 AN: 41562

American (AMR) AF: 0.0418 AC: 640 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.125 AC: 647 AN: 5182

South Asian (SAS) AF: 0.0875 AC: 423 AN: 4832

European-Finnish (FIN) AF: 0.0174 AC: 185 AN: 10606

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1674 AN: 68020

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0283 Hom.: 121

Bravo AF: 0.0382

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Birt-Hogg-Dube syndrome (1)
-	-	1	Familial spontaneous pneumothorax (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12602675; hg19: chr17-17116576;