rs7218992

Variant names:

• chr17-17212319-C-A
• rs7218992
• NM_144997.7:c.*1336G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-17212319-C-A
• chr17-17212319-C-G
• chr17-17212319-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.*1336G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 175,982 control chromosomes in the GnomAD database, including 1,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1193 hom., cov: 28)
  • Exomes 𝑓: 0.11 (181 hom.)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.956
• Publications: 7 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=-0.79).
• BP6: Variant 17-17212319-C-A is Benign according to our data. Variant chr17-17212319-C-A is described in ClinVar as Benign. ClinVar VariationId is 322034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 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.*1336G>T		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*1336G>T		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*1336G>T		3_prime_UTR	Exon 15 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.*1336G>T		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2666G>T		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*1336G>T		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18390 AN: 151430 Hom.: 1190 Cov.: 28

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.108 AC: 2640 AN: 24434 Hom.: 181 Cov.: 0 AF XY: 0.111 AC XY: 1242 AN XY: 11214

African (AFR) AF: 0.105 AC: 84 AN: 800

American (AMR) AF: 0.0923 AC: 48 AN: 520

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 230 AN: 1516

East Asian (EAS) AF: 0.0113 AC: 60 AN: 5308

South Asian (SAS) AF: 0.107 AC: 22 AN: 206

European-Finnish (FIN) AF: 0.0556 AC: 1 AN: 18

Middle Eastern (MID) AF: 0.146 AC: 24 AN: 164

European-Non Finnish (NFE) AF: 0.137 AC: 1916 AN: 13964

Other (OTH) AF: 0.132 AC: 255 AN: 1938

GnomAD4 genome AF: 0.121 AC: 18410 AN: 151548 Hom.: 1193 Cov.: 28 AF XY: 0.120 AC XY: 8865 AN XY: 74062

African (AFR) AF: 0.115 AC: 4745 AN: 41258

American (AMR) AF: 0.107 AC: 1633 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3466

East Asian (EAS) AF: 0.00349 AC: 18 AN: 5158

South Asian (SAS) AF: 0.0647 AC: 311 AN: 4806

European-Finnish (FIN) AF: 0.111 AC: 1155 AN: 10452

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.140 AC: 9512 AN: 67902

Other (OTH) AF: 0.134 AC: 280 AN: 2086

Alfa AF: 0.116 Hom.: 445

Bravo AF: 0.123

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Birt-Hogg-Dube syndrome (1)
-	-	1	Familial spontaneous pneumothorax (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.65
PhyloP100		0.96
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: rs7218992; hg19: chr17-17115633;