rs148582447

chr4-103110950-G-Achr4-103110950-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001813.3(CENPE):c.7602C>T(p.Ser2534=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,610,262 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: CENPE NM_001813.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.81

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-103110950-G-A is Benign according to our data. Variant chr4-103110950-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPE	NM_001813.3	c.7602C>T	p.Ser2534=	synonymous_variant	47/49	ENST00000265148.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPE	ENST00000265148.9	c.7602C>T	p.Ser2534=	synonymous_variant	47/49	2	NM_001813.3	A2
CENPE	ENST00000380026.8	c.7239C>T	p.Ser2413=	synonymous_variant	45/47	1		P2

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 241 AN: 151960 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00194 AC: 482 AN: 249092 Hom.: 0 AF XY: 0.00195 AC XY: 262 AN XY: 134678

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00185

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00133 AC: 1935 AN: 1458184 Hom.: 5 Cov.: 30 AF XY: 0.00137 AC XY: 997 AN XY: 725436

Gnomad4 AFR exome AF: 0.000960

Gnomad4 AMR exome AF: 0.00225

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00167

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00108

Gnomad4 OTH exome AF: 0.00213

GnomAD4 genome AF: 0.00158 AC: 240 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74348

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00146

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00216 Hom.: 1

Bravo AF: 0.00182

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 05, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.58
Dann	Benign	0.49

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: rs148582447; hg19: chr4-104032107;