rs117577125
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001458.5(FLNC):c.2122-27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,612,762 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0051 ( 29 hom. )
Consequence
FLNC
NM_001458.5 intron
NM_001458.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.19
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 made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 7-128842204-T-C is Benign according to our data. Variant chr7-128842204-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128842204-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00349 (531/152262) while in subpopulation NFE AF= 0.00638 (434/68010). AF 95% confidence interval is 0.00589. There are 3 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 531 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.2122-27T>C | intron_variant | ENST00000325888.13 | |||
FLNC | NM_001127487.2 | c.2122-27T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.2122-27T>C | intron_variant | 1 | NM_001458.5 | P3 | |||
FLNC | ENST00000346177.6 | c.2122-27T>C | intron_variant | 1 | A1 | ||||
FLNC | ENST00000388853.3 | n.238-27T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00349 AC: 531AN: 152144Hom.: 3 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
531
AN:
152144
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00340 AC: 836AN: 246222Hom.: 2 AF XY: 0.00350 AC XY: 470AN XY: 134122
GnomAD3 exomes
AF:
AC:
836
AN:
246222
Hom.:
AF XY:
AC XY:
470
AN XY:
134122
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00506 AC: 7385AN: 1460500Hom.: 29 Cov.: 33 AF XY: 0.00501 AC XY: 3640AN XY: 726504
GnomAD4 exome
AF:
AC:
7385
AN:
1460500
Hom.:
Cov.:
33
AF XY:
AC XY:
3640
AN XY:
726504
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00349 AC: 531AN: 152262Hom.: 3 Cov.: 33 AF XY: 0.00310 AC XY: 231AN XY: 74436
GnomAD4 genome
?
AF:
AC:
531
AN:
152262
Hom.:
Cov.:
33
AF XY:
AC XY:
231
AN XY:
74436
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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