chr4-103106487-G-A

Position:

• chr4-103106487-G-A

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.8012-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,132 control chromosomes in the GnomAD database, including 2,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2311 hom., cov: 32)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.976

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=-0.87).
• BP6: Variant 4-103106487-G-A is Benign according to our data. Variant chr4-103106487-G-A is described in ClinVar as [Benign]. Clinvar id is 1290610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPE	NM_001813.3	c.8012-171C>T		intron_variant		ENST00000265148.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPE	ENST00000265148.9	c.8012-171C>T		intron_variant		2	NM_001813.3	A2
CENPE	ENST00000380026.8	c.7649-171C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25617 AN: 152012 Hom.: 2312 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.169 AC: 25641 AN: 152132 Hom.: 2311 Cov.: 32 AF XY: 0.170 AC XY: 12677 AN XY: 74372

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.180

Alfa AF: 0.170 Hom.: 355

Bravo AF: 0.168

Asia WGS AF: 0.230 AC: 800 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	-0.87
CADD	Benign	10
DANN	Benign	0.69

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: rs17215862; hg19: chr4-104027644;