12-53277765-A-G
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_012291.5(ESPL1):c.2225-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,596,634 control chromosomes in the GnomAD database, including 329,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.59 ( 27454 hom., cov: 31)
Exomes 𝑓: 0.64 ( 302214 hom. )
Consequence
ESPL1
NM_012291.5 intron
NM_012291.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.14
Genes affected
ESPL1 (HGNC:16856): (extra spindle pole bodies like 1, separase) Stable cohesion between sister chromatids before anaphase and their timely separation during anaphase are critical for chromosome inheritance. In vertebrates, sister chromatid cohesion is released in 2 steps via distinct mechanisms. The first step involves phosphorylation of STAG1 (MIM 604358) or STAG2 (MIM 300826) in the cohesin complex. The second step involves cleavage of the cohesin subunit SCC1 (RAD21; MIM 606462) by ESPL1, or separase, which initiates the final separation of sister chromatids (Sun et al., 2009 [PubMed 19345191]).[supplied by OMIM, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPL1 | NM_012291.5 | c.2225-56A>G | intron_variant | ENST00000257934.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPL1 | ENST00000257934.9 | c.2225-56A>G | intron_variant | 5 | NM_012291.5 | P1 | |||
ESPL1 | ENST00000552671.5 | c.*2156-56A>G | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.591 AC: 89829AN: 151882Hom.: 27432 Cov.: 31
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GnomAD4 exome AF: 0.644 AC: 930795AN: 1444634Hom.: 302214 Cov.: 32 AF XY: 0.648 AC XY: 464564AN XY: 717010
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GnomAD4 genome AF: 0.591 AC: 89878AN: 152000Hom.: 27454 Cov.: 31 AF XY: 0.595 AC XY: 44232AN XY: 74300
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
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