rs878855215

Variant names:

• chr17-17213726-G-A
• rs878855215
• NM_144997.7:c.1669C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-17213726-G-A
• chr17-17213726-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_144997.7(FLCN):​c.1669C>T​(p.Leu557Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L557L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLCN NM_144997.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.76
• Publications: 0 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 -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 17-17213726-G-A is Benign according to our data. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17213726-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7	c.1669C>T	p.Leu557Leu	synonymous_variant	Exon 14 of 14	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.1669C>T	p.Leu557Leu	synonymous_variant	Exon 14 of 14	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.*372+1259C>T		intron_variant	Intron 9 of 11	1		ENSP00000394249.3
MPRIP	ENST00000578209.5	c.*18-3764G>A		intron_variant	Intron 5 of 5	3		ENSP00000464276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Birt-Hogg-Dube syndrome 1 Benign:1

Oct 28, 2024

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Hereditary cancer-predisposing syndrome Benign:1

Mar 19, 2020

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Birt-Hogg-Dube syndrome Benign:1

Jun 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.5
DANN	Benign	0.86
PhyloP100		2.8

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: rs878855215; hg19: chr17-17117040;