7-128842386-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001458.5(FLNC):c.2265+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,613,054 control chromosomes in the GnomAD database, including 12,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4050 hom., cov: 33)

Exomes 𝑓: 0.078 ( 8941 hom. )

Consequence

FLNC
NM_001458.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.07

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-128842386-C-G is Benign according to our data. Variant chr7-128842386-C-G is described in ClinVar as [Benign]. Clinvar id is 226640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128842386-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNC	NM_001458.5 link	c.2265+12C>G		intron_variant	Intron 14 of 47	ENST00000325888.13	NP_001449.3	Q14315-1Q59H94
FLNC	NM_001127487.2 link	c.2265+12C>G		intron_variant	Intron 14 of 46		NP_001120959.1	Q14315-2Q59H94

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FLNC	ENST00000325888.13 link	c.2265+12C>G	intron_variant	Intron 14 of 47	1	NM_001458.5	ENSP00000327145.8	Q14315-1
FLNC	ENST00000346177.6 link	c.2265+12C>G	intron_variant	Intron 14 of 46	1		ENSP00000344002.6	Q14315-2
FLNC	ENST00000388853.3 link	n.381+12C>G	intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25633

AN:

152046

Hom.:

4037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0351

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0532

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.126

AC:

31075

AN:

247176

Hom.:

3672

AF XY:

0.118

AC XY:

15945

AN XY:

134576

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.362

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0406

Gnomad NFE exome

AF:

0.0536

Gnomad OTH exome

AF:

0.0939

GnomAD4 exome

AF:

0.0779

AC:

113798

AN:

1460890

Hom.:

8941

Cov.:

AF XY:

0.0789

AC XY:

57341

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.406

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.0188

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.0413

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.0952

GnomAD4 genome

AF:

0.169

AC:

25676

AN:

152164

Hom.:

4050

Cov.:

AF XY:

0.167

AC XY:

12453

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.0351

Gnomad4 NFE

AF:

0.0532

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0346

Hom.:

Bravo

AF:

0.185

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2265+12C>G in intron 14 of FLNC: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence. It has been identified in 36.7% (1523/4152) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs2291566). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 12, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 08, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.92

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over