4-103108588-CTAAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001813.3(CENPE):c.8011+211_8011+214del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,960 control chromosomes in the GnomAD database, including 2,296 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2296 hom., cov: 28)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.898

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 -10 ACMG points.

• BP6: Variant 4-103108588-CTAAA-C is Benign according to our data. Variant chr4-103108588-CTAAA-C is described in ClinVar as [Benign]. Clinvar id is 1259061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPE	NM_001813.3	c.8011+211_8011+214del		intron_variant		ENST00000265148.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPE	ENST00000265148.9	c.8011+211_8011+214del		intron_variant		2	NM_001813.3	A2
CENPE	ENST00000380026.8	c.7648+211_7648+214del		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24461 AN: 151842 Hom.: 2294 Cov.: 28

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24471 AN: 151960 Hom.: 2296 Cov.: 28 AF XY: 0.164 AC XY: 12181 AN XY: 74234

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.167

Alfa AF: 0.191 Hom.: 382

Bravo AF: 0.148

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs142557236; hg19: chr4-104029745;