Variant rs2291567 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001458.5(FLNC):c.2551-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,501,336 control chromosomes in the GnomAD database, including 34,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 7436 hom., cov: 33)

Exomes 𝑓: 0.19 ( 26920 hom. )

Consequence

FLNC
NM_001458.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.659

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=-0.89).

BP6

Variant 7-128843173-T-C is Benign according to our data. Variant chr7-128843173-T-C is described in ClinVar as [Benign]. Clinvar id is 1236146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNC	NM_001458.5 linkuse as main transcript	c.2551-56T>C		intron_variant		ENST00000325888.13	NP_001449.3
FLNC	NM_001127487.2 linkuse as main transcript	c.2551-56T>C		intron_variant			NP_001120959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNC	ENST00000325888.13 linkuse as main transcript	c.2551-56T>C		intron_variant		1	NM_001458.5	ENSP00000327145	P3	Q14315-1
FLNC	ENST00000346177.6 linkuse as main transcript	c.2551-56T>C		intron_variant		1		ENSP00000344002	A1	Q14315-2

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41124

AN:

151938

Hom.:

7414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.185

AC:

249745

AN:

1349280

Hom.:

26920

Cov.:

AF XY:

0.186

AC XY:

124460

AN XY:

668938

show subpopulations

Gnomad4 AFR exome

AF:

0.504

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.271

AC:

41182

AN:

152056

Hom.:

7436

Cov.:

AF XY:

0.268

AC XY:

19915

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.468

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.180

Hom.:

3749

Bravo

AF:

0.285

Asia WGS

AF:

0.383

AC:

1330

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.2

DANN

Benign

0.43

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