chr7-128846392-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001458.5(FLNC):c.4056C>T(p.Arg1352Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,611,006 control chromosomes in the GnomAD database, including 5,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 1043 hom., cov: 33)

Exomes 𝑓: 0.053 ( 4134 hom. )

Consequence

FLNC
NM_001458.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -8.61

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-128846392-C-T is Benign according to our data. Variant chr7-128846392-C-T is described in ClinVar as [Benign]. Clinvar id is 129089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128846392-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-8.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNC	NM_001458.5 link	c.4056C>T	p.Arg1352Arg	synonymous_variant	Exon 23 of 48	ENST00000325888.13	NP_001449.3	Q14315-1Q59H94
FLNC	NM_001127487.2 link	c.4056C>T	p.Arg1352Arg	synonymous_variant	Exon 23 of 47		NP_001120959.1	Q14315-2Q59H94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNC	ENST00000325888.13 link	c.4056C>T	p.Arg1352Arg	synonymous_variant	Exon 23 of 48	1	NM_001458.5	ENSP00000327145.8		Q14315-1
FLNC	ENST00000346177.6 link	c.4056C>T	p.Arg1352Arg	synonymous_variant	Exon 23 of 47	1		ENSP00000344002.6		Q14315-2

Frequencies

GnomAD3 genomes

AF:

0.0895

AC:

13616

AN:

152072

Hom.:

1038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0897

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.0939

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0766

GnomAD3 exomes

AF:

0.0888

AC:

21928

AN:

247042

Hom.:

1885

AF XY:

0.0827

AC XY:

11114

AN XY:

134336

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.328

Gnomad SAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.0264

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0707

GnomAD4 exome

AF:

0.0531

AC:

77424

AN:

1458816

Hom.:

4134

Cov.:

AF XY:

0.0532

AC XY:

38649

AN XY:

725858

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.0844

Gnomad4 FIN exome

AF:

0.0273

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0608

GnomAD4 genome

AF:

0.0896

AC:

13632

AN:

152190

Hom.:

1043

Cov.:

AF XY:

0.0901

AC XY:

6708

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.0894

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.0936

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0385

Gnomad4 OTH

AF:

0.0762

Alfa

AF:

0.0559

Hom.:

212

Bravo

AF:

0.102

Asia WGS

AF:

0.173

AC:

601

AN:

3478

EpiCase

AF:

0.0359

EpiControl

AF:

0.0395

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Feb 12, 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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Arg1352Arg in exon 23 of FLNC: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 15.9% (661/4150) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs75770585). -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 10, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 13, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 24, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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. -

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

Benign:1

Feb 04, 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

-0.88

CADD

Benign

0.032

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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