rs2720460

Positions:

• chr4-103133529-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001813.3(CENPE):​c.6720+166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,006 control chromosomes in the GnomAD database, including 9,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9714 hom., cov: 31)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.944

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 4-103133529-A-G is Benign according to our data. Variant chr4-103133529-A-G is described in ClinVar as [Benign]. Clinvar id is 1288419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPE	NM_001813.3	c.6720+166T>C		intron_variant		ENST00000265148.9	NP_001804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9	c.6720+166T>C		intron_variant		2	NM_001813.3	ENSP00000265148	A2
CENPE	ENST00000380026.8	c.6357+166T>C		intron_variant		1		ENSP00000369365	P2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53788 AN: 151888 Hom.: 9709 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.354 AC: 53835 AN: 152006 Hom.: 9714 Cov.: 31 AF XY: 0.358 AC XY: 26607 AN XY: 74294

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.371

Alfa AF: 0.381 Hom.: 22833

Bravo AF: 0.344

Asia WGS AF: 0.357 AC: 1244 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 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.67

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: rs2720460; hg19: chr4-104054686;