dbSNP rs12530507: FLNC:c.6004+19G>A (chr7-128852771-G-A) – 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.6004+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,613,312 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 17 hom., cov: 33)

Exomes 𝑓: 0.017 ( 266 hom. )

Consequence

FLNC
NM_001458.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.159

Publications

2 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=-0.84).

BP6

Variant 7-128852771-G-A is Benign according to our data. Variant chr7-128852771-G-A is described in ClinVar as Benign. ClinVar VariationId is 258152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0118 (1798/152318) while in subpopulation NFE AF = 0.0189 (1286/68026). AF 95% confidence interval is 0.018. There are 17 homozygotes in GnomAd4. There are 834 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1798 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.6004+19G>A	intron	N/A	NP_001449.3	Q14315-1
FLNC	NM_001127487.2		c.5905+19G>A	intron	N/A	NP_001120959.1	Q14315-2
FLNC-AS1	NR_149055.1		n.215+514C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLNC	ENST00000325888.13	TSL:1 MANE Select	c.6004+19G>A	intron	N/A	ENSP00000327145.8	Q14315-1
FLNC	ENST00000346177.6	TSL:1	c.5905+19G>A	intron	N/A	ENSP00000344002.6	Q14315-2
FLNC	ENST00000950263.1		c.5902+19G>A	intron	N/A	ENSP00000620322.1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1798

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.0118

AC:

2933

AN:

248958

AF XY:

0.0116

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.00893

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0171

AC:

25051

AN:

1460994

Hom.:

266

Cov.:

AF XY:

0.0164

AC XY:

11893

AN XY:

726780

show subpopulations

African (AFR)

AF:

0.00308

AC:

103

AN:

33478

American (AMR)

AF:

0.00917

AC:

410

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000995

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.00130

AC:

112

AN:

86252

European-Finnish (FIN)

AF:

0.0171

AC:

904

AN:

52854

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0204

AC:

22683

AN:

1111738

Other (OTH)

AF:

0.0133

AC:

805

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1536

3072

4608

6144

7680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.0118

AC:

1798

AN:

152318

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

834

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00431

AC:

179

AN:

41568

American (AMR)

AF:

0.00981

AC:

150

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0152

AC:

161

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0189

AC:

1286

AN:

68026

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

189

283

378

472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0127

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (3)

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

-0.84

CADD

Benign

1.1

(source)

DANN

Benign

0.47

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism

(source)

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

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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