rs12506065

Positions:

• chr4-103121854-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001813.3(CENPE):​c.7143+1017G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,118 control chromosomes in the GnomAD database, including 1,945 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 0.15 (1945 hom., cov: 31)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPE	NM_001813.3	c.7143+1017G>T		intron_variant		ENST00000265148.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPE	ENST00000265148.9	c.7143+1017G>T		intron_variant		2	NM_001813.3	A2
CENPE	ENST00000380026.8	c.6780+1017G>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22276 AN: 152000 Hom.: 1947 Cov.: 31

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.146 AC: 22278 AN: 152118 Hom.: 1945 Cov.: 31 AF XY: 0.148 AC XY: 11029 AN XY: 74348

Gnomad4 AFR AF: 0.0580

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.164

Alfa AF: 0.157 Hom.: 323

Bravo AF: 0.143

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.83

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: rs12506065; hg19: chr4-104043011;