rs74009720

Variant names:

Variant summary

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

The ENST00000560563.2(ACTC1):n.2303C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 419,096 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 64 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 12 hom. )

Consequence

ACTC1
ENST00000560563.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0340

Publications

1 publications found

Variant links:

Genes affected

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

GJD2-DT links:

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 11
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
atrial septal defect 5
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
dilated cardiomyopathy 1R
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
arthrogryposis syndrome
Inheritance: AD Classification: MODERATE Submitted by: University of Washington Center for Rare Disease Research (UW-CRDR)
dilated cardiomyopathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACTC1 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 15-34790143-G-A is Benign according to our data. Variant chr15-34790143-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 315697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560563.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GJD2-DT	NR_120329.1		n.299+12712G>A	intron	N/A
ACTC1	NM_005159.5	MANE Select	c.*269C>T	downstream_gene	N/A	NP_005150.1	P68032
ACTC1	NM_001406482.1		c.*269C>T	downstream_gene	N/A	NP_001393411.1	P68032

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GJD2-DT	ENST00000558707.4	TSL:3	n.658G>A	non_coding_transcript_exon	Exon 3 of 3
ACTC1	ENST00000560563.2	TSL:2	n.2303C>T	non_coding_transcript_exon	Exon 6 of 6
GJD2-DT	ENST00000693120.3		n.497G>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2458

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00215

AC:

575

AN:

266874

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

268

AN XY:

142006

show subpopulations

African (AFR)

AF:

0.0538

AC:

446

AN:

8284

American (AMR)

AF:

0.00271

AC:

AN:

12924

Ashkenazi Jewish (ASJ)

AF:

0.000127

AC:

AN:

7868

East Asian (EAS)

AF:

0.00

AC:

AN:

16114

South Asian (SAS)

AF:

0.000275

AC:

AN:

36402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12726

Middle Eastern (MID)

AF:

0.00455

AC:

AN:

1100

European-Non Finnish (NFE)

AF:

0.000204

AC:

AN:

156610

Other (OTH)

AF:

0.00310

AC:

AN:

14846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0162

AC:

2467

AN:

152222

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1177

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0572

AC:

2376

AN:

41512

American (AMR)

AF:

0.00380

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68026

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

120

240

361

481

601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0103

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dilated cardiomyopathy 1R (1)

Hypertrophic cardiomyopathy 11 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.63

PhyloP100

-0.034

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