dbSNP rs566679569: FLNC:c.7990+9C>T (chr7-128858226-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001458.5(FLNC):c.7990+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,413,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

FLNC
NM_001458.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.01

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-128858226-C-T is Benign according to our data. Variant chr7-128858226-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 387017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000738 (112/151852) while in subpopulation AFR AF = 0.00174 (72/41382). AF 95% confidence interval is 0.00142. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 112 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLNC	NM_001458.5	MANE Select	c.7990+9C>T	intron	N/A	NP_001449.3	Q14315-1
FLNC	NM_001127487.2		c.7891+9C>T	intron	N/A	NP_001120959.1	Q14315-2
FLNC-AS1	NR_149055.1		n.102+4299G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLNC	ENST00000325888.13	TSL:1 MANE Select	c.7990+9C>T	intron	N/A	ENSP00000327145.8	Q14315-1
FLNC	ENST00000346177.6	TSL:1	c.7891+9C>T	intron	N/A	ENSP00000344002.6	Q14315-2
FLNC	ENST00000950263.1		c.7888+9C>T	intron	N/A	ENSP00000620322.1

Frequencies

GnomAD3 genomes

AF:

0.000738

AC:

112

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000367

AC:

AN:

201886

AF XY:

0.000326

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.000702

Gnomad ASJ exome

AF:

0.000223

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.000583

GnomAD4 exome

AF:

0.000346

AC:

436

AN:

1261242

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

222

AN XY:

636676

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

30354

American (AMR)

AF:

0.000919

AC:

AN:

43538

Ashkenazi Jewish (ASJ)

AF:

0.000162

AC:

AN:

24704

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38562

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81844

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52210

Middle Eastern (MID)

AF:

0.00197

AC:

AN:

4578

European-Non Finnish (NFE)

AF:

0.000297

AC:

277

AN:

931950

Other (OTH)

AF:

0.00101

AC:

AN:

53502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.000738

AC:

112

AN:

151852

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.00174

AC:

AN:

41382

American (AMR)

AF:

0.00144

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67908

Other (OTH)

AF:

0.00143

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000485

Hom.:

Bravo

AF:

0.00110

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (3)

Cardiomyopathy (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: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.29

(source)

DANN

Benign

0.79

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over