rs141538225
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000224784.10(ACTA2):c.78C>T(p.Asp26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,613,930 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 0.00031 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 1 hom. )
Consequence
ACTA2
ENST00000224784.10 synonymous
ENST00000224784.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.38
Genes affected
ACTA2 (HGNC:130): (actin alpha 2, smooth muscle) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome. [provided by RefSeq, Sep 2017]
STAMBPL1 (HGNC:24105): (STAM binding protein like 1) Predicted to enable Lys63-specific deubiquitinase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein K63-linked deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 10-88948853-G-A is Benign according to our data. Variant chr10-88948853-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.38 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000309 (47/152224) while in subpopulation AFR AF= 0.00104 (43/41538). AF 95% confidence interval is 0.000789. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 47 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTA2 | NM_001613.4 | c.78C>T | p.Asp26= | synonymous_variant | 2/9 | ENST00000224784.10 | NP_001604.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTA2 | ENST00000224784.10 | c.78C>T | p.Asp26= | synonymous_variant | 2/9 | 1 | NM_001613.4 | ENSP00000224784 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152106Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000151 AC: 38AN: 251074Hom.: 1 AF XY: 0.000155 AC XY: 21AN XY: 135672
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461706Hom.: 1 Cov.: 30 AF XY: 0.0000371 AC XY: 27AN XY: 727142
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GnomAD4 genome AF: 0.000309 AC: 47AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 05, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 11, 2023 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
Aortic aneurysm, familial thoracic 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 09, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at