rs4985705

Variant names:

• chr17-17217354-G-A
• rs4985705
• NM_144997.7:c.1063-172C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-17217354-G-A
• chr17-17217354-G-C
• chr17-17217354-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001353229.2(FLCN):​c.1117-172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 505,082 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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)
  • Exomes 𝑓: 0.000012 (1 hom.)
• Consequence: FLCN NM_001353229.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 10 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353229.2. 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.1063-172C>T		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1117-172C>T		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1063-172C>T		intron	N/A	NP_001340159.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	ENST00000285071.9	TSL:1 MANE Select	c.1063-172C>T		intron	N/A	ENSP00000285071.4
	ENSG00000264187	ENST00000427497.3	TSL:1	n.185-172C>T		intron	N/A	ENSP00000394249.3
	FLCN	ENST00000962729.1		c.1168-172C>T		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000119 AC: 6 AN: 505082 Hom.: 1 AF XY: 0.0000111 AC XY: 3 AN XY: 270626

African (AFR) AF: 0.00 AC: 0 AN: 14142

American (AMR) AF: 0.00 AC: 0 AN: 29240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17590

East Asian (EAS) AF: 0.00 AC: 0 AN: 31498

South Asian (SAS) AF: 0.00 AC: 0 AN: 55850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2466

European-Non Finnish (NFE) AF: 0.0000204 AC: 6 AN: 294072

Other (OTH) AF: 0.00 AC: 0 AN: 28418

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.066
DANN	Benign	0.57
PhyloP100		-2.2

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: rs4985705; hg19: chr17-17120668;