dbSNP rs2272313: ESPL1:c.2225-56A>G (chr12-53277765-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

17 publications found

Variant links:

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]

ESPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ESPL1	NM_012291.5 link	c.2225-56A>G		intron_variant	Intron 10 of 30	ENST00000257934.9	NP_036423.4	Q14674-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESPL1	ENST00000257934.9 link	c.2225-56A>G		intron_variant	Intron 10 of 30	5	NM_012291.5	ENSP00000257934.4		Q14674-1
ESPL1	ENST00000552671.5 link	n.*2156-56A>G		intron_variant	Intron 10 of 30	2		ENSP00000447054.1		H3BM31

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89829

AN:

151882

Hom.:

27432

Cov.:

show subpopulations

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.:

AF XY:

0.648

AC XY:

464564

AN XY:

717010

show subpopulations

African (AFR)

AF:

0.424

AC:

14029

AN:

33108

American (AMR)

AF:

0.645

AC:

28084

AN:

43522

Ashkenazi Jewish (ASJ)

AF:

0.702

AC:

17480

AN:

24912

East Asian (EAS)

AF:

0.812

AC:

32115

AN:

39528

South Asian (SAS)

AF:

0.737

AC:

62192

AN:

84370

European-Finnish (FIN)

AF:

0.664

AC:

35130

AN:

52880

Middle Eastern (MID)

AF:

0.683

AC:

3856

AN:

5644

European-Non Finnish (NFE)

AF:

0.635

AC:

699448

AN:

1101078

Other (OTH)

AF:

0.645

AC:

38461

AN:

59592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17649

35299

52948

70598

88247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18720

37440

56160

74880

93600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.591

AC:

89878

AN:

152000

Hom.:

27454

Cov.:

AF XY:

0.595

AC XY:

44232

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.438

AC:

18134

AN:

41426

American (AMR)

AF:

0.596

AC:

9099

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

2368

AN:

3468

East Asian (EAS)

AF:

0.810

AC:

4182

AN:

5160

South Asian (SAS)

AF:

0.750

AC:

3620

AN:

4824

European-Finnish (FIN)

AF:

0.673

AC:

7116

AN:

10578

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.638

AC:

43321

AN:

67952

Other (OTH)

AF:

0.604

AC:

1275

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1856

3713

5569

7426

9282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.628

Hom.:

16643

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

(source)

DANN

Benign

0.50

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over