17-17212475-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAA

Variant names:

• chr17-17212475-T-TAA
• rs397932764
• NM_144997.7:c.*1178_*1179dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_144997.7(FLCN):​c.*1178_*1179dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0057 (18 hom., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00566 (424/74960) while in subpopulation AFR AF = 0.0208 (376/18038). AF 95% confidence interval is 0.0191. There are 18 homozygotes in GnomAd4. There are 200 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High AC in GnomAd4 at 424 AD gene.

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.*1178_*1179dupTT		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*1178_*1179dupTT		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*1178_*1179dupTT		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.*1178_*1179dupTT		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2508_*372+2509dupTT		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*1178_*1179dupTT		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 424 AN: 74934 Hom.: 18 Cov.: 19

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00349

Gnomad ASJ AF: 0.000957

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00237

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00781

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.00328

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1068 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 536

African (AFR) AF: 0.00 AC: 0 AN: 36

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 54

East Asian (EAS) AF: 0.00 AC: 0 AN: 376

South Asian (SAS) AF: 0.00 AC: 0 AN: 10

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 494

Other (OTH) AF: 0.00 AC: 0 AN: 72

GnomAD4 genome AF: 0.00566 AC: 424 AN: 74960 Hom.: 18 Cov.: 19 AF XY: 0.00582 AC XY: 200 AN XY: 34348

African (AFR) AF: 0.0208 AC: 376 AN: 18038

American (AMR) AF: 0.00348 AC: 22 AN: 6320

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 2 AN: 2090

East Asian (EAS) AF: 0.00 AC: 0 AN: 2960

South Asian (SAS) AF: 0.00238 AC: 5 AN: 2104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2758

Middle Eastern (MID) AF: 0.00833 AC: 1 AN: 120

European-Non Finnish (NFE) AF: 0.000383 AC: 15 AN: 39140

Other (OTH) AF: 0.00325 AC: 3 AN: 924

Alfa AF: 0.00 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397932764; hg19: chr17-17115789;