chr17-17216447-C-T

Variant names:

• chr17-17216447-C-T
• rs61750032
• NM_144997.7:c.1233G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_144997.7(FLCN):​c.1233G>A​(p.Glu411Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 1,613,828 control chromosomes in the GnomAD database, including 514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (247 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (267 hom.)
• Consequence: FLCN NM_144997.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:19
• Conservation: PhyloP100: 1.21
• Publications: 6 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 17-17216447-C-T is Benign according to our data. Variant chr17-17216447-C-T is described in ClinVar as Benign. ClinVar VariationId is 96474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.1233G>A	p.Glu411Glu	synonymous	Exon 11 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.1287G>A	p.Glu429Glu	synonymous	Exon 13 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.1233G>A	p.Glu411Glu	synonymous	Exon 12 of 15	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.1233G>A	p.Glu411Glu	synonymous	Exon 11 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*67G>A		non_coding_transcript_exon	Exon 7 of 12	ENSP00000394249.3	J3QW42
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*67G>A		3_prime_UTR	Exon 7 of 12	ENSP00000394249.3	J3QW42

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5023 AN: 152162 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.00265

Gnomad OTH AF: 0.0297

GnomAD2 exomes AF: 0.0105 AC: 2616 AN: 249546 AF XY: 0.00805

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00286

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.00529 AC: 7730 AN: 1461548 Hom.: 267 Cov.: 31 AF XY: 0.00478 AC XY: 3479 AN XY: 727082

African (AFR) AF: 0.113 AC: 3796 AN: 33460

American (AMR) AF: 0.0132 AC: 591 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000418 AC: 36 AN: 86220

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53370

Middle Eastern (MID) AF: 0.0271 AC: 156 AN: 5762

European-Non Finnish (NFE) AF: 0.00211 AC: 2350 AN: 1111856

Other (OTH) AF: 0.0122 AC: 738 AN: 60378

GnomAD4 genome AF: 0.0330 AC: 5032 AN: 152280 Hom.: 247 Cov.: 32 AF XY: 0.0317 AC XY: 2363 AN XY: 74468

African (AFR) AF: 0.108 AC: 4481 AN: 41546

American (AMR) AF: 0.0185 AC: 284 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00265 AC: 180 AN: 68008

Other (OTH) AF: 0.0294 AC: 62 AN: 2108

Alfa AF: 0.0168 Hom.: 59

Bravo AF: 0.0382

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.00393

EpiControl AF: 0.00439

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	4	not provided (4)
-	-	3	Birt-Hogg-Dube syndrome (3)
-	-	2	Birt-Hogg-Dube syndrome 1 (2)
-	-	1	Familial spontaneous pneumothorax (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	6.9
DANN	Benign	0.90
PhyloP100		1.2
Mutation Taster		=94/6	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: rs61750032; hg19: chr17-17119761;