rs7208065

Variant names:

• chr17-17216890-T-A
• rs7208065
• NM_144997.7:c.1176+179A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-17216890-T-A
• chr17-17216890-T-C
• chr17-17216890-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144997.7(FLCN):​c.1176+179A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 511,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000020 (0 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.1176+179A>T		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1230+179A>T		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1176+179A>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.1176+179A>T		intron	N/A	ENSP00000285071.4
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*10+179A>T		intron	N/A	ENSP00000394249.3
	FLCN	ENST00000962729.1		c.1281+179A>T		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000196 AC: 1 AN: 511168 Hom.: 0 AF XY: 0.00000366 AC XY: 1 AN XY: 272876

African (AFR) AF: 0.00 AC: 0 AN: 14756

American (AMR) AF: 0.00 AC: 0 AN: 30558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17450

East Asian (EAS) AF: 0.00 AC: 0 AN: 31476

South Asian (SAS) AF: 0.00 AC: 0 AN: 56524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2254

European-Non Finnish (NFE) AF: 0.00000337 AC: 1 AN: 297036

Other (OTH) AF: 0.00 AC: 0 AN: 28532

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.83
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7208065; hg19: chr17-17120204;