rs2272313

chr12-53277765-A-Gchr12-53277765-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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]

ACMG classification

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: 89829 AN: 151882 Hom.: 27432 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.644 AC: 930795 AN: 1444634 Hom.: 302214 Cov.: 32 AF XY: 0.648 AC XY: 464564 AN XY: 717010

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.645

Gnomad4 ASJ exome AF: 0.702

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.664

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.591 AC: 89878 AN: 152000 Hom.: 27454 Cov.: 31 AF XY: 0.595 AC XY: 44232 AN XY: 74300

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.604

Alfa AF: 0.630 Hom.: 15048

Bravo AF: 0.576

Asia WGS AF: 0.763 AC: 2653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.27
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2272313; hg19: chr12-53671549;