rs117653869

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001458.5(FLNC):c.6004+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 1,613,252 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 72 hom. )

Consequence

FLNC
NM_001458.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.0660

Variant links:

Genes affected

FLNC (HGNC:3756): (filamin C) This gene encodes one of three related filamin genes, specifically gamma filamin. These filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. Three functional domains exist in filamin: an N-terminal filamentous actin-binding domain, a C-terminal self-association domain, and a membrane glycoprotein-binding domain. Mutations in this gene are a cause of cardiopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2022]

FLNC links:

FLNC-AS1 (HGNC:53474): (FLNC antisense RNA 1)

FLNC-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-128852763-G-A is Benign according to our data. Variant chr7-128852763-G-A is described in ClinVar as [Benign]. Clinvar id is 258151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128852763-G-A is described in Lovd as [Benign]. Variant chr7-128852763-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00705 (1074/152248) while in subpopulation NFE AF= 0.0112 (759/67986). AF 95% confidence interval is 0.0105. There are 7 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1074 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FLNC	NM_001458.5 link	c.6004+11G>A	intron_variant	Intron 36 of 47	ENST00000325888.13	NP_001449.3	Q14315-1Q59H94
FLNC	NM_001127487.2 link	c.5905+11G>A	intron_variant	Intron 35 of 46		NP_001120959.1	Q14315-2Q59H94
FLNC-AS1	NR_149055.1 link	n.215+522C>T	intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FLNC	ENST00000325888.13 link	c.6004+11G>A	intron_variant	Intron 36 of 47	1	NM_001458.5	ENSP00000327145.8	Q14315-1
FLNC	ENST00000346177.6 link	c.5905+11G>A	intron_variant	Intron 35 of 46	1		ENSP00000344002.6	Q14315-2
FLNC-AS1	ENST00000469965.1 link	n.215+522C>T	intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

1075

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00981

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00717

AC:

1786

AN:

249034

Hom.:

AF XY:

0.00710

AC XY:

960

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.00389

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00469

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.00844

GnomAD4 exome

AF:

0.00953

AC:

13923

AN:

1461004

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

6720

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00698

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.00464

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00820

GnomAD4 genome

AF:

0.00705

AC:

1074

AN:

152248

Hom.:

Cov.:

AF XY:

0.00647

AC XY:

482

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.00739

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 02, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FLNC: BS1, BS2 -

Nov 07, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.85

CADD

Benign

0.55

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over