rs370589662

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001458.5(FLNC):c.6702C>G(p.Phe2234Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,455,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. F2234F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FLNC
NM_001458.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.729

Publications

0 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 links:

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

FLNC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 7-128854191-C-G is Benign according to our data. Variant chr7-128854191-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1446278.

BS2

High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNC	NM_001458.5 link	c.6702C>G	p.Phe2234Leu	missense_variant	Exon 40 of 48	ENST00000325888.13	NP_001449.3	Q14315-1Q59H94
FLNC	NM_001127487.2 link	c.6603C>G	p.Phe2201Leu	missense_variant	Exon 39 of 47		NP_001120959.1	Q14315-2Q59H94
FLNC-AS1	NR_149055.1 link	n.103-794G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNC	ENST00000325888.13 link	c.6702C>G	p.Phe2234Leu	missense_variant	Exon 40 of 48	1	NM_001458.5	ENSP00000327145.8		Q14315-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000413

AC:

AN:

241936

AF XY:

0.00000756

show subpopulations

Gnomad AFR exome

AF:

0.0000673

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1455840

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1109542

Other (OTH)

AF:

0.00

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Uncertain:1

May 01, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.F2234L variant (also known as c.6702C>G), located in coding exon 40 of the FLNC gene, results from a C to G substitution at nucleotide position 6702. The phenylalanine at codon 2234 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

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

Benign:1

Aug 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

8.4

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.1

L;.

PhyloP100

-0.73

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.95

N;N

REVEL

Uncertain

0.61

Sift

Benign

0.72

T;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.42

B;B

Vest4

0.79

MutPred

0.79

Loss of sheet (P = 0.1158);.;

MVP

0.92

MPC

0.83

ClinPred

0.085

GERP RS

-4.5

Varity_R

0.042

gMVP

0.59

Mutation Taster

=49/51

disease causing

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over