rs12506065

Variant names:

• chr4-103121854-C-A
• rs12506065
• NM_001813.3:c.7143+1017G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

CENPE Gene-Disease associations (from GenCC):

• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• microcephaly 13, primary, autosomal recessive

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001813.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPE	NM_001813.3	MANE Select	c.7143+1017G>T		intron	N/A	NP_001804.2	Q02224-1
	CENPE	NM_001286734.2		c.6780+1017G>T		intron	N/A	NP_001273663.1	Q02224-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPE	ENST00000265148.9	TSL:2 MANE Select	c.7143+1017G>T		intron	N/A	ENSP00000265148.3	Q02224-1
	CENPE	ENST00000380026.8	TSL:1	c.6780+1017G>T		intron	N/A	ENSP00000369365.3	Q02224-3
	CENPE	ENST00000933323.1		c.7146+1017G>T		intron	N/A	ENSP00000603382.1

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

African (AFR) AF: 0.0580 AC: 2408 AN: 41524

American (AMR) AF: 0.197 AC: 3003 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.140 AC: 724 AN: 5186

South Asian (SAS) AF: 0.303 AC: 1461 AN: 4814

European-Finnish (FIN) AF: 0.121 AC: 1284 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12107 AN: 67956

Other (OTH) AF: 0.164 AC: 347 AN: 2116

Alfa AF: 0.155 Hom.: 330

Bravo AF: 0.143

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.83
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12506065; hg19: chr4-104043011;