chr7-128846309-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001458.5(FLNC):c.3973C>T(p.Leu1325Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,613,268 control chromosomes in the GnomAD database, including 36,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 8234 hom., cov: 33)

Exomes 𝑓: 0.18 ( 28004 hom. )

Consequence

FLNC
NM_001458.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.393

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, ClinGen, Ambry Genetics
myofibrillar myopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
myofibrillar myopathy 5
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy 26
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
distal myopathy with posterior leg and anterior hand involvement
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
familial isolated restrictive cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
heart conduction disease
Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp

FLNC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 7-128846309-C-T is Benign according to our data. Variant chr7-128846309-C-T is described in ClinVar as Benign. ClinVar VariationId is 129088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.393 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001458.5. 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
	FLNC	NM_001458.5	MANE Select	c.3973C>T	p.Leu1325Leu	synonymous	Exon 23 of 48	NP_001449.3	Q14315-1
	FLNC	NM_001127487.2		c.3973C>T	p.Leu1325Leu	synonymous	Exon 23 of 47	NP_001120959.1	Q14315-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLNC	ENST00000325888.13	TSL:1 MANE Select	c.3973C>T	p.Leu1325Leu	synonymous	Exon 23 of 48	ENSP00000327145.8	Q14315-1
FLNC	ENST00000346177.6	TSL:1	c.3973C>T	p.Leu1325Leu	synonymous	Exon 23 of 47	ENSP00000344002.6	Q14315-2
FLNC	ENST00000950263.1		c.3970C>T	p.Leu1324Leu	synonymous	Exon 23 of 47	ENSP00000620322.1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42645

AN:

151926

Hom.:

8201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.249

GnomAD2 exomes

AF:

0.219

AC:

54420

AN:

248170

AF XY:

0.211

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.423

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.181

AC:

264678

AN:

1461224

Hom.:

28004

Cov.:

AF XY:

0.181

AC XY:

131491

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.553

AC:

18514

AN:

33478

American (AMR)

AF:

0.210

AC:

9390

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3713

AN:

26126

East Asian (EAS)

AF:

0.420

AC:

16667

AN:

39676

South Asian (SAS)

AF:

0.201

AC:

17339

AN:

86234

European-Finnish (FIN)

AF:

0.169

AC:

8969

AN:

53172

Middle Eastern (MID)

AF:

0.146

AC:

844

AN:

5766

European-Non Finnish (NFE)

AF:

0.160

AC:

177489

AN:

1111762

Other (OTH)

AF:

0.195

AC:

11753

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13720

27440

41160

54880

68600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6584

13168

19752

26336

32920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.281

AC:

42729

AN:

152044

Hom.:

8234

Cov.:

AF XY:

0.279

AC XY:

20722

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.544

AC:

22523

AN:

41434

American (AMR)

AF:

0.191

AC:

2919

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

526

AN:

3472

East Asian (EAS)

AF:

0.425

AC:

2189

AN:

5150

South Asian (SAS)

AF:

0.217

AC:

1047

AN:

4820

European-Finnish (FIN)

AF:

0.165

AC:

1753

AN:

10612

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11127

AN:

67948

Other (OTH)

AF:

0.251

AC:

529

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1346

2692

4039

5385

6731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.221

Hom.:

10388

Bravo

AF:

0.298

Asia WGS

AF:

0.315

AC:

1094

AN:

3478

EpiCase

AF:

0.163

EpiControl

AF:

0.163

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

not provided (2)

Cardiovascular phenotype (1)

Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.5

(source)

DANN

Benign

0.84

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over