chr7-128852819-T-C

Position:

chr7-128852819-T-C

Variant summary

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

The NM_001458.5(FLNC):c.6005-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,613,792 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 169 hom. )

Consequence

FLNC
NM_001458.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0007572

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.181

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-128852819-T-C is Benign according to our data. Variant chr7-128852819-T-C is described in ClinVar as [Benign]. Clinvar id is 197000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128852819-T-C is described in Lovd as [Benign]. Variant chr7-128852819-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
FLNC	NM_001458.5 linkuse as main transcript	c.6005-9T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000325888.13	NP_001449.3
FLNC-AS1	NR_149055.1 linkuse as main transcript	n.215+466A>G	intron_variant, non_coding_transcript_variant
FLNC	NM_001127487.2 linkuse as main transcript	c.5906-9T>C	splice_polypyrimidine_tract_variant, intron_variant		NP_001120959.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
FLNC	ENST00000325888.13 linkuse as main transcript	c.6005-9T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001458.5	ENSP00000327145	P3	Q14315-1
FLNC	ENST00000346177.6 linkuse as main transcript	c.5906-9T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000344002	A1	Q14315-2
FLNC-AS1	ENST00000469965.1 linkuse as main transcript	n.215+466A>G	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00343

AC:

522

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.0583

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00822

AC:

2050

AN:

249370

Hom.:

AF XY:

0.00996

AC XY:

1348

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0173

Gnomad SAS exome

AF:

0.0503

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00429

GnomAD4 exome

AF:

0.00507

AC:

7410

AN:

1461508

Hom.:

169

Cov.:

AF XY:

0.00629

AC XY:

4576

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0189

Gnomad4 SAS exome

AF:

0.0499

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.00624

GnomAD4 genome

AF:

0.00340

AC:

518

AN:

152284

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

345

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0203

Gnomad4 SAS

AF:

0.0575

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00171

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 23, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

May 16, 2023

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00076

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.060

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