chr17-17215375-G-A

Variant names:

• chr17-17215375-G-A
• rs34311146
• NM_144997.7:c.1301-59C>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.1301-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,610,620 control chromosomes in the GnomAD database, including 25,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1718 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24111 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.99
• Publications: 4 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=-0.98).
• BP6: Variant 17-17215375-G-A is Benign according to our data. Variant chr17-17215375-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 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.1301-59C>T		intron	N/A	NP_659434.2
	FLCN	NM_001353229.2		c.1355-59C>T		intron	N/A	NP_001340158.1
	FLCN	NM_001353230.2		c.1301-59C>T		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.1301-59C>T		intron	N/A	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*135-59C>T		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.1406-59C>T		intron	N/A	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19766 AN: 152030 Hom.: 1722 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.174 AC: 253530 AN: 1458472 Hom.: 24111 AF XY: 0.172 AC XY: 125057 AN XY: 725598

African (AFR) AF: 0.0306 AC: 1023 AN: 33470

American (AMR) AF: 0.120 AC: 5352 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 6110 AN: 26132

East Asian (EAS) AF: 0.00239 AC: 95 AN: 39698

South Asian (SAS) AF: 0.0898 AC: 7731 AN: 86048

European-Finnish (FIN) AF: 0.127 AC: 6421 AN: 50626

Middle Eastern (MID) AF: 0.225 AC: 1295 AN: 5754

European-Non Finnish (NFE) AF: 0.194 AC: 215549 AN: 1111680

Other (OTH) AF: 0.165 AC: 9954 AN: 60344

GnomAD4 genome AF: 0.130 AC: 19752 AN: 152148 Hom.: 1718 Cov.: 32 AF XY: 0.123 AC XY: 9174 AN XY: 74380

African (AFR) AF: 0.0339 AC: 1407 AN: 41552

American (AMR) AF: 0.134 AC: 2053 AN: 15290

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

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5166

South Asian (SAS) AF: 0.0867 AC: 418 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1180 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13233 AN: 67958

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.108 Hom.: 298

Bravo AF: 0.129

Asia WGS AF: 0.0400 AC: 140 AN: 3478

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	-0.98
CADD	Benign	0.044
DANN	Benign	0.50
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs34311146; hg19: chr17-17118689;