rs55907818

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001458.5(FLNC):c.850+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 1,613,974 control chromosomes in the GnomAD database, including 6,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 515 hom., cov: 33)

Exomes 𝑓: 0.086 ( 5485 hom. )

Consequence

FLNC
NM_001458.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.50

Publications

6 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, Ambry Genetics, ClinGen
myofibrillar myopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
myofibrillar myopathy 5
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
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: Ambry Genetics, Orphanet
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

new If you want to explore the variant's impact on the transcript NM_001458.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-128837566-G-A is Benign according to our data. Variant chr7-128837566-G-A is described in ClinVar as Benign. ClinVar VariationId is 258154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.086 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.850+18G>A		intron	N/A	NP_001449.3	Q14315-1
	FLNC	NM_001127487.2		c.850+18G>A		intron	N/A	NP_001120959.1	Q14315-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLNC	ENST00000325888.13	TSL:1 MANE Select	c.850+18G>A	intron	N/A	ENSP00000327145.8	Q14315-1
FLNC	ENST00000346177.6	TSL:1	c.850+18G>A	intron	N/A	ENSP00000344002.6	Q14315-2
FLNC	ENST00000950263.1		c.850+18G>A	intron	N/A	ENSP00000620322.1

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12304

AN:

152192

Hom.:

517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0504

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.0870

Gnomad SAS

AF:

0.0928

Gnomad FIN

AF:

0.0629

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0873

Gnomad OTH

AF:

0.0961

GnomAD2 exomes

AF:

0.0789

AC:

19679

AN:

249328

AF XY:

0.0808

show subpopulations

Gnomad AFR exome

AF:

0.0838

Gnomad AMR exome

AF:

0.0384

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0725

Gnomad FIN exome

AF:

0.0684

Gnomad NFE exome

AF:

0.0882

Gnomad OTH exome

AF:

0.0903

GnomAD4 exome

AF:

0.0858

AC:

125360

AN:

1461664

Hom.:

5485

Cov.:

AF XY:

0.0862

AC XY:

62649

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.0826

AC:

2766

AN:

33480

American (AMR)

AF:

0.0420

AC:

1877

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2734

AN:

26136

East Asian (EAS)

AF:

0.0942

AC:

3740

AN:

39700

South Asian (SAS)

AF:

0.0879

AC:

7585

AN:

86258

European-Finnish (FIN)

AF:

0.0711

AC:

3788

AN:

53242

Middle Eastern (MID)

AF:

0.0820

AC:

473

AN:

5768

European-Non Finnish (NFE)

AF:

0.0874

AC:

97210

AN:

1111968

Other (OTH)

AF:

0.0859

AC:

5187

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

7765

15531

23296

31062

38827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3592

7184

10776

14368

17960

<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:

0.0809

AC:

12315

AN:

152310

Hom.:

515

Cov.:

AF XY:

0.0792

AC XY:

5897

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0804

AC:

3342

AN:

41554

American (AMR)

AF:

0.0502

AC:

769

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

397

AN:

3470

East Asian (EAS)

AF:

0.0872

AC:

452

AN:

5184

South Asian (SAS)

AF:

0.0931

AC:

450

AN:

4832

European-Finnish (FIN)

AF:

0.0629

AC:

668

AN:

10624

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0873

AC:

5940

AN:

68016

Other (OTH)

AF:

0.0984

AC:

208

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

606

1211

1817

2422

3028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0886

Hom.:

161

Bravo

AF:

0.0803

Asia WGS

AF:

0.101

AC:

352

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.015

(source)

DANN

Benign

0.46

PhyloP100

-3.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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