Genetic Variant ACTC1:c.808+76G>C (chr15-34792014-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005159.5(ACTC1):c.808+76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,525,606 control chromosomes in the GnomAD database, including 58,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5161 hom., cov: 33)

Exomes 𝑓: 0.28 ( 53710 hom. )

Consequence

ACTC1
NM_005159.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.702

Publications

9 publications found

Variant links:

Genes affected

ACTC1 (HGNC:143): (actin alpha cardiac muscle 1) Actins are highly conserved proteins that are involved in various types of cell motility. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The protein encoded by this gene belongs to the actin family which is comprised of three main groups of actin isoforms, alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Defects in this gene have been associated with idiopathic dilated cardiomyopathy (IDC) and familial hypertrophic cardiomyopathy (FHC). [provided by RefSeq, Jul 2008]

ACTC1 links:

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

GJD2-DT 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 15-34792014-C-G is Benign according to our data. Variant chr15-34792014-C-G is described in ClinVar as Benign. ClinVar VariationId is 1292062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTC1	NM_005159.5	MANE Select	c.808+76G>C	intron	N/A	NP_005150.1	P68032
ACTC1	NM_001406482.1		c.808+76G>C	intron	N/A	NP_001393411.1	P68032
ACTC1	NM_001406483.1		c.808+76G>C	intron	N/A	NP_001393412.1	P68032

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTC1	ENST00000290378.6	TSL:1 MANE Select	c.808+76G>C	intron	N/A	ENSP00000290378.4	P68032
ACTC1	ENST00000713613.1		c.919+76G>C	intron	N/A	ENSP00000518909.1	A0AAQ5BGG2
ACTC1	ENST00000868408.1		c.814+76G>C	intron	N/A	ENSP00000538467.1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38489

AN:

152018

Hom.:

5158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.276

AC:

379105

AN:

1373470

Hom.:

53710

Cov.:

AF XY:

0.278

AC XY:

190899

AN XY:

686918

show subpopulations

African (AFR)

AF:

0.159

AC:

5035

AN:

31608

American (AMR)

AF:

0.376

AC:

16259

AN:

43198

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

6572

AN:

25400

East Asian (EAS)

AF:

0.360

AC:

14033

AN:

39032

South Asian (SAS)

AF:

0.334

AC:

27859

AN:

83474

European-Finnish (FIN)

AF:

0.250

AC:

13074

AN:

52400

Middle Eastern (MID)

AF:

0.297

AC:

1224

AN:

4122

European-Non Finnish (NFE)

AF:

0.270

AC:

279815

AN:

1036838

Other (OTH)

AF:

0.265

AC:

15234

AN:

57398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13901

27801

41702

55602

69503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9266

18532

27798

37064

46330

<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:

0.253

AC:

38496

AN:

152136

Hom.:

5161

Cov.:

AF XY:

0.255

AC XY:

18940

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.164

AC:

6794

AN:

41530

American (AMR)

AF:

0.345

AC:

5276

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

889

AN:

3468

East Asian (EAS)

AF:

0.342

AC:

1761

AN:

5154

South Asian (SAS)

AF:

0.334

AC:

1609

AN:

4812

European-Finnish (FIN)

AF:

0.252

AC:

2663

AN:

10584

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18445

AN:

67980

Other (OTH)

AF:

0.259

AC:

547

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1485

2969

4454

5938

7423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.249

Hom.:

604

Bravo

AF:

0.255

Asia WGS

AF:

0.334

AC:

1160

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.56

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(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