17-17217030-C-T

Variant names:

• chr17-17217030-C-T
• rs41424546
• NM_144997.7:c.1176+39G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144997.7(FLCN):​c.1176+39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,444,410 control chromosomes in the GnomAD database, including 12,717 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: 𝑓 0.10 (957 hom., cov: 33)
  • Exomes 𝑓: 0.13 (11760 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

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+39G>A		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1230+39G>A		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1176+39G>A		intron	N/A	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.1176+39G>A		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*10+39G>A		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.1281+39G>A		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15742 AN: 152130 Hom.: 956 Cov.: 33

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.116 AC: 28784 AN: 247374 AF XY: 0.119

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.000328

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.130 AC: 168320 AN: 1292162 Hom.: 11760 Cov.: 19 AF XY: 0.131 AC XY: 85069 AN XY: 651640

African (AFR) AF: 0.0382 AC: 1143 AN: 29946

American (AMR) AF: 0.130 AC: 5754 AN: 44302

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3856 AN: 25034

East Asian (EAS) AF: 0.000206 AC: 8 AN: 38886

South Asian (SAS) AF: 0.124 AC: 10253 AN: 82672

European-Finnish (FIN) AF: 0.117 AC: 6177 AN: 52996

Middle Eastern (MID) AF: 0.139 AC: 747 AN: 5368

European-Non Finnish (NFE) AF: 0.139 AC: 133647 AN: 958276

Other (OTH) AF: 0.123 AC: 6735 AN: 54682

GnomAD4 genome AF: 0.103 AC: 15752 AN: 152248 Hom.: 957 Cov.: 33 AF XY: 0.104 AC XY: 7719 AN XY: 74450

African (AFR) AF: 0.0421 AC: 1749 AN: 41560

American (AMR) AF: 0.121 AC: 1855 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.109 AC: 526 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10602

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9379 AN: 68012

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.0774 Hom.: 129

Bravo AF: 0.101

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.42
DANN	Benign	0.53
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs41424546; hg19: chr17-17120344; COSMIC: COSV53259737;