chr10-88941407-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001613.4(ACTA2):c.455-17G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 1,613,720 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0084 ( 43 hom., cov: 32)
Exomes 𝑓: 0.0084 ( 354 hom. )
Consequence
ACTA2
NM_001613.4 splice_polypyrimidine_tract, intron
NM_001613.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.325
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 10-88941407-C-T is Benign according to our data. Variant chr10-88941407-C-T is described in ClinVar as [Benign]. Clinvar id is 35644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-88941407-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTA2 | NM_001613.4 | c.455-17G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000224784.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTA2 | ENST00000224784.10 | c.455-17G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001613.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00836 AC: 1271AN: 151998Hom.: 43 Cov.: 32
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GnomAD3 exomes AF: 0.0146 AC: 3656AN: 250896Hom.: 163 AF XY: 0.0145 AC XY: 1970AN XY: 135580
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GnomAD4 exome AF: 0.00842 AC: 12305AN: 1461606Hom.: 354 Cov.: 31 AF XY: 0.00873 AC XY: 6348AN XY: 727110
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GnomAD4 genome ? AF: 0.00839 AC: 1276AN: 152114Hom.: 43 Cov.: 32 AF XY: 0.00923 AC XY: 686AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 21, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Familial aortopathy Benign:1
Benign, criteria provided, single submitter | curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Aortic aneurysm, familial thoracic 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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