chr17-37089042-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_198834.3(ACACA):c.6924G>A(p.Ala2308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,614,180 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 2 hom. )
Consequence
ACACA
NM_198834.3 synonymous
NM_198834.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.149
Genes affected
ACACA (HGNC:84): (acetyl-CoA carboxylase alpha) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
Variant 17-37089042-C-T is Benign according to our data. Variant chr17-37089042-C-T is described in ClinVar as [Benign]. Clinvar id is 559339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.149 with no splicing effect.
BS2
High AC in GnomAd4 at 417 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACACA | NM_198834.3 | c.6924G>A | p.Ala2308= | synonymous_variant | 55/56 | ENST00000616317.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACACA | ENST00000616317.5 | c.6924G>A | p.Ala2308= | synonymous_variant | 55/56 | 1 | NM_198834.3 |
Frequencies
GnomAD3 genomes AF: 0.00273 AC: 416AN: 152180Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000616 AC: 155AN: 251470Hom.: 0 AF XY: 0.000441 AC XY: 60AN XY: 135910
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GnomAD4 exome AF: 0.000270 AC: 395AN: 1461882Hom.: 2 Cov.: 32 AF XY: 0.000223 AC XY: 162AN XY: 727246
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GnomAD4 genome AF: 0.00274 AC: 417AN: 152298Hom.: 2 Cov.: 32 AF XY: 0.00286 AC XY: 213AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 15, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
ACACA-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 19, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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