4-103108582-G-C

Position:

• chr4-103108582-G-C

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.8011+221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 146,592 control chromosomes in the GnomAD database, including 1,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1942 hom., cov: 32)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

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=-0.88).
• BP6: Variant 4-103108582-G-C is Benign according to our data. Variant chr4-103108582-G-C is described in ClinVar as [Benign]. Clinvar id is 1231699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPE	NM_001813.3	c.8011+221C>G		intron_variant		ENST00000265148.9	NP_001804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9	c.8011+221C>G		intron_variant		2	NM_001813.3	ENSP00000265148	A2
CENPE	ENST00000380026.8	c.7648+221C>G		intron_variant		1		ENSP00000369365	P2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22219 AN: 146478 Hom.: 1944 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.152 AC: 22220 AN: 146592 Hom.: 1942 Cov.: 32 AF XY: 0.154 AC XY: 11000 AN XY: 71394

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.171

Alfa AF: 0.156 Hom.: 200

Bravo AF: 0.143

Asia WGS AF: 0.226 AC: 771 AN: 3410

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.8
DANN	Benign	0.37

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: rs72665048; hg19: chr4-104029739;