rs769303249
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_005159.5(ACTC1):c.309C>T(p.His103His) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000372 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ACTC1
NM_005159.5 synonymous
NM_005159.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.05
Publications
1 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 15-34793390-G-A is Benign according to our data. Variant chr15-34793390-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 416058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACTC1 | NM_005159.5 | MANE Select | c.309C>T | p.His103His | synonymous | Exon 3 of 7 | NP_005150.1 | ||
| ACTC1 | NM_001406482.1 | c.309C>T | p.His103His | synonymous | Exon 2 of 6 | NP_001393411.1 | |||
| ACTC1 | NM_001406483.1 | c.309C>T | p.His103His | synonymous | Exon 3 of 7 | NP_001393412.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACTC1 | ENST00000290378.6 | TSL:1 MANE Select | c.309C>T | p.His103His | synonymous | Exon 3 of 7 | ENSP00000290378.4 | ||
| ACTC1 | ENST00000713613.1 | c.420C>T | p.His140His | synonymous | Exon 4 of 8 | ENSP00000518909.1 | |||
| ACTC1 | ENST00000713610.1 | c.309C>T | p.His103His | synonymous | Exon 3 of 7 | ENSP00000518905.1 |
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
152130
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251492 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251492
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727248 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1461894
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727248
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
2
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60396
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74306 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
152130
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74306
show subpopulations
African (AFR)
AF:
AC:
4
AN:
41426
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cardiomyopathy Benign:1
Oct 14, 2019
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Hypertrophic cardiomyopathy 11;C2748552:Atrial septal defect 5;C3150681:Dilated cardiomyopathy 1R Benign:1
Nov 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Hypertrophic cardiomyopathy Benign:1
Aug 13, 2024
All of Us Research Program, National Institutes of Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Cardiovascular phenotype Benign:1
May 27, 2023
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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