10-88938205-G-A
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001613.4(ACTA2):c.846C>T(p.Asn282=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000409 in 1,614,020 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 0.000085 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
ACTA2
NM_001613.4 synonymous
NM_001613.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.30
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]
ACTA2-AS1 (HGNC:45169): (ACTA2 antisense RNA 1)
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 -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 10-88938205-G-A is Benign according to our data. Variant chr10-88938205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 536920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000854 (13/152260) while in subpopulation AMR AF= 0.000523 (8/15298). AF 95% confidence interval is 0.00026. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTA2 | NM_001613.4 | c.846C>T | p.Asn282= | synonymous_variant | 8/9 | ENST00000224784.10 | NP_001604.1 | |
ACTA2-AS1 | NR_125373.1 | n.1199-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTA2 | ENST00000224784.10 | c.846C>T | p.Asn282= | synonymous_variant | 8/9 | 1 | NM_001613.4 | ENSP00000224784 | P1 | |
ACTA2-AS1 | ENST00000437930.4 | n.1240-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152142Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 251092Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135686
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727184
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152260Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
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 | Nov 18, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 27, 2020 | 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 | Feb 05, 2024 | - - |
ACTA2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 31, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Aortic aneurysm, familial thoracic 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 25, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at