rs34235236

Variant names:

• chr17-17215128-T-C
• rs34235236
• NM_144997.7:c.1433-38A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-17215128-T-C
• chr17-17215128-T-A
• chr17-17215128-T-G

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.1433-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,376 control chromosomes in the GnomAD database, including 58,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.22 (4034 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54466 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.802
• Publications: 11 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: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-17215128-T-C is Benign according to our data. Variant chr17-17215128-T-C is described in ClinVar as Benign. ClinVar VariationId is 253253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 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.1433-38A>G		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1487-38A>G		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1433-38A>G		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.1433-38A>G		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*267-38A>G		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.1538-38A>G		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32662 AN: 151540 Hom.: 4028 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.00296

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.235

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.233 AC: 58535 AN: 251172 AF XY: 0.237

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.266 AC: 388239 AN: 1461722 Hom.: 54466 Cov.: 41 AF XY: 0.265 AC XY: 192483 AN XY: 727138

African (AFR) AF: 0.106 AC: 3535 AN: 33480

American (AMR) AF: 0.232 AC: 10395 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6026 AN: 26136

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39700

South Asian (SAS) AF: 0.237 AC: 20458 AN: 86256

European-Finnish (FIN) AF: 0.281 AC: 14952 AN: 53300

Middle Eastern (MID) AF: 0.231 AC: 1331 AN: 5768

European-Non Finnish (NFE) AF: 0.285 AC: 316585 AN: 1111970

Other (OTH) AF: 0.247 AC: 14936 AN: 60388

GnomAD4 genome AF: 0.216 AC: 32692 AN: 151654 Hom.: 4034 Cov.: 32 AF XY: 0.217 AC XY: 16048 AN XY: 74092

African (AFR) AF: 0.112 AC: 4641 AN: 41366

American (AMR) AF: 0.230 AC: 3507 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3472

East Asian (EAS) AF: 0.00297 AC: 15 AN: 5058

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4814

European-Finnish (FIN) AF: 0.284 AC: 3004 AN: 10560

Middle Eastern (MID) AF: 0.231 AC: 66 AN: 286

European-Non Finnish (NFE) AF: 0.276 AC: 18701 AN: 67834

Other (OTH) AF: 0.235 AC: 495 AN: 2110

Alfa AF: 0.205 Hom.: 1036

Bravo AF: 0.205

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Birt-Hogg-Dube syndrome (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.98
DANN	Benign	0.40
PhyloP100		-0.80
BranchPoint Hunter		4.0
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: rs34235236; hg19: chr17-17118442; COSMIC: COSV53257291;