rs41371953

Variant names:

• chr17-17216935-C-G
• rs41371953
• NM_144997.7:c.1176+134G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-17216935-C-G
• chr17-17216935-C-A
• chr17-17216935-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144997.7(FLCN):​c.1176+134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 731,558 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (159 hom., cov: 33)
  • Exomes 𝑓: 0.021 (188 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.921
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-17216935-C-G is Benign according to our data. Variant chr17-17216935-C-G is described in ClinVar as Benign. ClinVar VariationId is 1292842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0749 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+134G>C		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1230+134G>C		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1176+134G>C		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+134G>C		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*10+134G>C		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.1281+134G>C		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5340 AN: 152156 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0215 AC: 12430 AN: 579284 Hom.: 188 Cov.: 7 AF XY: 0.0210 AC XY: 6504 AN XY: 310386

African (AFR) AF: 0.0800 AC: 1299 AN: 16246

American (AMR) AF: 0.0134 AC: 463 AN: 34570

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 600 AN: 19970

East Asian (EAS) AF: 0.00938 AC: 302 AN: 32182

South Asian (SAS) AF: 0.0213 AC: 1340 AN: 62850

European-Finnish (FIN) AF: 0.00468 AC: 187 AN: 39918

Middle Eastern (MID) AF: 0.0348 AC: 87 AN: 2502

European-Non Finnish (NFE) AF: 0.0217 AC: 7361 AN: 339950

Other (OTH) AF: 0.0254 AC: 791 AN: 31096

GnomAD4 genome AF: 0.0351 AC: 5342 AN: 152274 Hom.: 159 Cov.: 33 AF XY: 0.0341 AC XY: 2536 AN XY: 74462

African (AFR) AF: 0.0772 AC: 3205 AN: 41540

American (AMR) AF: 0.0198 AC: 303 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3466

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.0188 AC: 91 AN: 4828

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1515 AN: 68028

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.00324 Hom.: 0

Bravo AF: 0.0375

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		-0.92
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: rs41371953; hg19: chr17-17120249;