rs2291561

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.795T>C(p.Gly265Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,614,090 control chromosomes in the GnomAD database, including 10,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 993 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9412 hom. )

Consequence

FLNC
NM_001458.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -9.97

Publications

15 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: ClinGen, Ambry Genetics, G2P
myofibrillar myopathy 5
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P
hypertrophic cardiomyopathy 26
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
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=-0.78).

BP6

Variant 7-128837493-T-C is Benign according to our data. Variant chr7-128837493-T-C is described in ClinVar as Benign. ClinVar VariationId is 129099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 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.795T>C	p.Gly265Gly	synonymous	Exon 4 of 48	NP_001449.3
	FLNC	NM_001127487.2		c.795T>C	p.Gly265Gly	synonymous	Exon 4 of 47	NP_001120959.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FLNC	ENST00000325888.13	TSL:1 MANE Select	c.795T>C	p.Gly265Gly	synonymous	Exon 4 of 48	ENSP00000327145.8
FLNC	ENST00000346177.6	TSL:1	c.795T>C	p.Gly265Gly	synonymous	Exon 4 of 47	ENSP00000344002.6
FLNC	ENST00000950263.1		c.795T>C	p.Gly265Gly	synonymous	Exon 4 of 47	ENSP00000620322.1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16805

AN:

152164

Hom.:

994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0804

Gnomad AMR

AF:

0.0616

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0962

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.105

AC:

26225

AN:

249778

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0471

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0944

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.112

AC:

163888

AN:

1461808

Hom.:

9412

Cov.:

AF XY:

0.113

AC XY:

82280

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.123

AC:

4130

AN:

33476

American (AMR)

AF:

0.0518

AC:

2318

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2815

AN:

26136

East Asian (EAS)

AF:

0.116

AC:

4598

AN:

39700

South Asian (SAS)

AF:

0.141

AC:

12204

AN:

86256

European-Finnish (FIN)

AF:

0.103

AC:

5478

AN:

53398

Middle Eastern (MID)

AF:

0.0865

AC:

499

AN:

5768

European-Non Finnish (NFE)

AF:

0.112

AC:

125003

AN:

1111960

Other (OTH)

AF:

0.113

AC:

6843

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9963

19926

29888

39851

49814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4588

9176

13764

18352

22940

<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:

0.111

AC:

16830

AN:

152282

Hom.:

993

Cov.:

AF XY:

0.109

AC XY:

8152

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.122

AC:

5049

AN:

41542

American (AMR)

AF:

0.0615

AC:

941

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

575

AN:

5180

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4828

European-Finnish (FIN)

AF:

0.0962

AC:

1021

AN:

10616

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7735

AN:

68030

Other (OTH)

AF:

0.125

AC:

264

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

789

1578

2367

3156

3945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.111

Hom.:

1487

Bravo

AF:

0.107

Asia WGS

AF:

0.151

AC:

525

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.111

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

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

-0.78

CADD

Benign

0.46

(source)

DANN

Benign

0.65

PhyloP100

-10

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