rs377164890
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_004153.4(ORC1):āc.1239A>Cā(p.Ala413=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,614,160 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 (ā ā ).
Frequency
Genomes: š 0.00018 ( 0 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
ORC1
NM_004153.4 synonymous
NM_004153.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.774
Genes affected
ORC1 (HGNC:8487): (origin recognition complex subunit 1) The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the ORC complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MyST2/HBO1), a protein involved in control of transcription silencing. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 1-52388586-T-G is Benign according to our data. Variant chr1-52388586-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 129855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.774 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000148 (216/1461820) while in subpopulation MID AF= 0.00262 (15/5728). AF 95% confidence interval is 0.00161. There are 0 homozygotes in gnomad4_exome. There are 118 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ORC1 | NM_004153.4 | c.1239A>C | p.Ala413= | synonymous_variant | 8/17 | ENST00000371568.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ORC1 | ENST00000371568.8 | c.1239A>C | p.Ala413= | synonymous_variant | 8/17 | 1 | NM_004153.4 | P1 | |
ORC1 | ENST00000371566.1 | c.1239A>C | p.Ala413= | synonymous_variant | 8/17 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 251490Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135920
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GnomAD4 exome AF: 0.000148 AC: 216AN: 1461820Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 118AN XY: 727210
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 17, 2013 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2023 | - - |
Computational scores
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Name
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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