17-17227933-C-G

Position:

• chr17-17227933-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144997.7(FLCN):​c.205G>C​(p.Val69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLCN NM_144997.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043669045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7	c.205G>C	p.Val69Leu	missense_variant	4/14	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.205G>C	p.Val69Leu	missense_variant	4/14	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.148+57G>C		intron_variant		1		ENSP00000394249.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.73
DANN	Benign	0.90
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.86	D;T;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.14
MutPred		0.18		Gain of relative solvent accessibility (P = 0.1066);Gain of relative solvent accessibility (P = 0.1066);.;
MVP		0.39
MPC		0.36
ClinPred		0.13	T
GERP RS		-0.45
Varity_R		0.031
gMVP		0.077

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-17131247; COSMIC: COSV53261992; COSMIC: COSV53261992;