chr7-128850850-GACA-G
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_001458.5(FLNC):c.5451_5453delCAA(p.Asn1817del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
FLNC
NM_001458.5 disruptive_inframe_deletion
NM_001458.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.29
Publications
0 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001458.5. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High AC in GnomAdExome4 at 17 AD gene.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FLNC | NM_001458.5 | MANE Select | c.5451_5453delCAA | p.Asn1817del | disruptive_inframe_deletion | Exon 33 of 48 | NP_001449.3 | ||
| FLNC | NM_001127487.2 | c.5352_5354delCAA | p.Asn1784del | disruptive_inframe_deletion | Exon 32 of 47 | NP_001120959.1 | |||
| FLNC-AS1 | NR_149055.1 | n.316-448_316-446delTGT | intron | N/A |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FLNC | ENST00000325888.13 | TSL:1 MANE Select | c.5451_5453delCAA | p.Asn1817del | disruptive_inframe_deletion | Exon 33 of 48 | ENSP00000327145.8 | ||
| FLNC | ENST00000346177.6 | TSL:1 | c.5352_5354delCAA | p.Asn1784del | disruptive_inframe_deletion | Exon 32 of 47 | ENSP00000344002.6 | ||
| FLNC | ENST00000714183.1 | c.5451_5453delCAA | p.Asn1817del | disruptive_inframe_deletion | Exon 33 of 47 | ENSP00000519472.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461634Hom.: 0 AF XY: 0.0000110 AC XY: 8AN XY: 727136 show subpopulations
GnomAD4 exome
AF:
AC:
17
AN:
1461634
Hom.:
AF XY:
AC XY:
8
AN XY:
727136
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
2
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53174
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
15
AN:
1112006
Other (OTH)
AF:
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
1
-
Cardiovascular phenotype (1)
-
1
-
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 (1)
-
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:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
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.