17-17213098-A-G

Variant names:

• chr17-17213098-A-G
• rs3803761
• NM_144997.7:c.*557T>C

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.*557T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 258,560 control chromosomes in the GnomAD database, including 66,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39164 hom., cov: 30)
  • Exomes 𝑓: 0.72 (27420 hom.)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.144
• Publications: 19 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=-0.88).
• BP6: Variant 17-17213098-A-G is Benign according to our data. Variant chr17-17213098-A-G is described in ClinVar as Benign. ClinVar VariationId is 322048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 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.*557T>C		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*557T>C		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*557T>C		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.*557T>C		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+1887T>C		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*557T>C		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108627 AN: 151904 Hom.: 39156 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.716 AC: 76274 AN: 106538 Hom.: 27420 Cov.: 0 AF XY: 0.713 AC XY: 36118 AN XY: 50646

African (AFR) AF: 0.651 AC: 2957 AN: 4544

American (AMR) AF: 0.709 AC: 4118 AN: 5808

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 3784 AN: 5548

East Asian (EAS) AF: 0.698 AC: 9284 AN: 13310

South Asian (SAS) AF: 0.677 AC: 2824 AN: 4174

European-Finnish (FIN) AF: 0.815 AC: 590 AN: 724

Middle Eastern (MID) AF: 0.634 AC: 350 AN: 552

European-Non Finnish (NFE) AF: 0.729 AC: 46667 AN: 63984

Other (OTH) AF: 0.722 AC: 5700 AN: 7894

GnomAD4 genome AF: 0.715 AC: 108678 AN: 152022 Hom.: 39164 Cov.: 30 AF XY: 0.719 AC XY: 53424 AN XY: 74310

African (AFR) AF: 0.657 AC: 27220 AN: 41440

American (AMR) AF: 0.699 AC: 10675 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2412 AN: 3468

East Asian (EAS) AF: 0.725 AC: 3744 AN: 5164

South Asian (SAS) AF: 0.664 AC: 3194 AN: 4812

European-Finnish (FIN) AF: 0.854 AC: 9045 AN: 10586

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.735 AC: 49987 AN: 67976

Other (OTH) AF: 0.690 AC: 1454 AN: 2106

Alfa AF: 0.727 Hom.: 173084

Bravo AF: 0.704

Asia WGS AF: 0.702 AC: 2438 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.88
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3803761; hg19: chr17-17116412;