chr17-17212475-T-TA

Position:

• chr17-17212475-T-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_144997.7(FLCN):​c.*1179_*1180insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.063 (600 hom., cov: 19)
  • Exomes 𝑓: 0.00094 (0 hom.)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.602

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]

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLCN	NM_144997.7	c.*1179_*1180insT		3_prime_UTR_variant	14/14	ENST00000285071.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLCN	ENST00000285071.9	c.*1179_*1180insT		3_prime_UTR_variant	14/14	1	NM_144997.7	P1
MPRIP	ENST00000578209.5	c.*18-4989dup		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 4742 AN: 74866 Hom.: 600 Cov.: 19

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00198

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0344

Gnomad EAS AF: 0.00877

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.00218

Gnomad MID AF: 0.0234

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.000936 AC: 1 AN: 1068 Hom.: 0 Cov.: 0 AF XY: 0.00187 AC XY: 1 AN XY: 536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0634 AC: 4748 AN: 74892 Hom.: 600 Cov.: 19 AF XY: 0.0628 AC XY: 2156 AN XY: 34308

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0344

Gnomad4 EAS AF: 0.00880

Gnomad4 SAS AF: 0.0386

Gnomad4 FIN AF: 0.00218

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0649

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Spontaneous pneumothorax Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Birt-Hogg-Dube syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs397932764; hg19: chr17-17115789;