Genetic Variant FLCN:c.*1179delT (chr17-17212475-TA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_144997.7(FLCN):c.*1179delT 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 0.0098 ( 7 hom., cov: 19)

Exomes 𝑓: 0.0056 ( 0 hom. )

Consequence

FLCN
NM_144997.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.602

Publications

0 publications found

Variant links:

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]

FLCN links:

ENSG00000264187 (HGNC:):

ENSG00000264187 links:

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]

MPRIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00979 (734/74958) while in subpopulation AMR AF = 0.0348 (220/6320). AF 95% confidence interval is 0.031. There are 7 homozygotes in GnomAd4. There are 325 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.

BS2

High AC in GnomAd4 at 734 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	NM_144997.7	MANE Select	c.*1179delT	3_prime_UTR	Exon 14 of 14	NP_659434.2
FLCN	NM_001353229.2		c.*1179delT	3_prime_UTR	Exon 16 of 16	NP_001340158.1
FLCN	NM_001353230.2		c.*1179delT	3_prime_UTR	Exon 15 of 15	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLCN	ENST00000285071.9	TSL:1 MANE Select	c.*1179delT	3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2509delT	intron	N/A	ENSP00000394249.3	J3QW42
FLCN	ENST00000962729.1		c.*1179delT	3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

734

AN:

74932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00661

Gnomad AMI

AF:

0.00198

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.00622

Gnomad EAS

AF:

0.0209

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.00109

Gnomad MID

AF:

0.00781

Gnomad NFE

AF:

0.00743

Gnomad OTH

AF:

0.0109

GnomAD4 exome

AF:

0.00562

AC:

AN:

1068

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

AN XY:

536

show subpopulations

African (AFR)

AF:

0.0278

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00532

AC:

AN:

376

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00405

AC:

AN:

494

Other (OTH)

AF:

0.0139

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00979

AC:

734

AN:

74958

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

325

AN XY:

34340

show subpopulations

African (AFR)

AF:

0.00659

AC:

119

AN:

18046

American (AMR)

AF:

0.0348

AC:

220

AN:

6320

Ashkenazi Jewish (ASJ)

AF:

0.00622

AC:

AN:

2090

East Asian (EAS)

AF:

0.0210

AC:

AN:

2958

South Asian (SAS)

AF:

0.00666

AC:

AN:

2102

European-Finnish (FIN)

AF:

0.00109

AC:

AN:

2758

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.00744

AC:

291

AN:

39134

Other (OTH)

AF:

0.0108

AC:

AN:

924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00118

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

17-17212475-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over