rs141650706

Variant names:

• chr17-17212699-T-C
• rs141650706
• NM_144997.7:c.*956A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144997.7(FLCN):​c.*956A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 181,614 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (128 hom., cov: 31)
  • Exomes 𝑓: 0.0071 (5 hom.)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.921
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 17-17212699-T-C is Benign according to our data. Variant chr17-17212699-T-C is described in ClinVar as Benign. ClinVar VariationId is 322040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 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.*956A>G		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*956A>G		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*956A>G		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.*956A>G		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2286A>G		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*956A>G		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3728 AN: 151654 Hom.: 127 Cov.: 31

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00261

Gnomad OTH AF: 0.0255

GnomAD4 exome AF: 0.00707 AC: 211 AN: 29842 Hom.: 5 Cov.: 0 AF XY: 0.00631 AC XY: 87 AN XY: 13796

African (AFR) AF: 0.0902 AC: 92 AN: 1020

American (AMR) AF: 0.0105 AC: 7 AN: 664

Ashkenazi Jewish (ASJ) AF: 0.00158 AC: 3 AN: 1898

East Asian (EAS) AF: 0.00 AC: 0 AN: 5930

South Asian (SAS) AF: 0.00 AC: 0 AN: 232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20

Middle Eastern (MID) AF: 0.0108 AC: 2 AN: 186

European-Non Finnish (NFE) AF: 0.00395 AC: 69 AN: 17458

Other (OTH) AF: 0.0156 AC: 38 AN: 2434

GnomAD4 genome AF: 0.0246 AC: 3737 AN: 151772 Hom.: 128 Cov.: 31 AF XY: 0.0240 AC XY: 1780 AN XY: 74160

African (AFR) AF: 0.0778 AC: 3216 AN: 41344

American (AMR) AF: 0.0175 AC: 267 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4798

European-Finnish (FIN) AF: 0.0000948 AC: 1 AN: 10544

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00261 AC: 177 AN: 67928

Other (OTH) AF: 0.0252 AC: 53 AN: 2104

Alfa AF: 0.0180 Hom.: 7

Bravo AF: 0.0292

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	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	-1.0
CADD	Benign	1.1
DANN	Benign	0.24
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism

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: rs141650706; hg19: chr17-17116013;