Genetic Variant CENPE:c.7724+16A>G (chr4-103110812-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001813.3(CENPE):c.7724+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000884 in 1,562,166 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 3 hom. )

Consequence

CENPE
NM_001813.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.46

Variant links:

Genes affected

CENPE (HGNC:1856): (centromere protein E) Centrosome-associated protein E (CENPE) is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centrosome-associated proteins, it is not present during interphase and first appears at the centromere region of chromosomes during prometaphase. This protein is required for stable spindle microtubule capture at kinetochores which is a necessary step in chromosome alignment during prometaphase. This protein also couples chromosome position to microtubule depolymerizing activity. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Nov 2014]

CENPE links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 4-103110812-T-C is Benign according to our data. Variant chr4-103110812-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1301481.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPE	NM_001813.3 link	c.7724+16A>G		intron_variant	Intron 47 of 48	ENST00000265148.9	NP_001804.2	Q02224-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9 link	c.7724+16A>G		intron_variant	Intron 47 of 48	2	NM_001813.3	ENSP00000265148.3		Q02224-1
CENPE	ENST00000380026.8 link	c.7361+16A>G		intron_variant	Intron 45 of 46	1		ENSP00000369365.3		Q02224-3

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

583

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00118

AC:

256

AN:

217240

AF XY:

0.000900

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000385

GnomAD4 exome

AF:

0.000562

AC:

792

AN:

1409812

Hom.:

Cov.:

AF XY:

0.000539

AC XY:

377

AN XY:

700028

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

AC:

361

AN:

31388

Gnomad4 AMR exome

AF:

0.000683

AC:

AN:

38072

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

23514

Gnomad4 EAS exome

AF:

0.0000256

AC:

AN:

39102

Gnomad4 SAS exome

AF:

0.0000128

AC:

AN:

77884

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

51740

Gnomad4 NFE exome

AF:

0.000305

AC:

331

AN:

1085278

Gnomad4 Remaining exome

AF:

0.00113

AC:

AN:

58204

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00387

AC:

589

AN:

152354

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

275

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0129

AC:

0.0128902

AN:

0.0128902

Gnomad4 AMR

AF:

0.00209

AC:

0.00209178

AN:

0.00209178

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000147

AC:

0.00014699

AN:

0.00014699

Gnomad4 OTH

AF:

0.00473

AC:

0.0047259

AN:

0.0047259

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00214

Hom.:

Bravo

AF:

0.00391

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 03, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.012

DANN

Benign

0.48

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over