rs2720460

Variant names:

• chr4-103133529-A-G
• rs2720460
• NM_001813.3:c.6720+166T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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 -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 VariationId 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 rank	MANE	Protein	UniProt
CENPE	NM_001813.3	c.6720+166T>C		intron_variant	Intron 41 of 48	ENST00000265148.9	NP_001804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9	c.6720+166T>C		intron_variant	Intron 41 of 48	2	NM_001813.3	ENSP00000265148.3
CENPE	ENST00000380026.8	c.6357+166T>C		intron_variant	Intron 39 of 46	1		ENSP00000369365.3

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

African (AFR) AF: 0.277 AC: 11489 AN: 41464

American (AMR) AF: 0.362 AC: 5533 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1542 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1527 AN: 5170

South Asian (SAS) AF: 0.417 AC: 2009 AN: 4816

European-Finnish (FIN) AF: 0.428 AC: 4513 AN: 10546

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26013 AN: 67954

Other (OTH) AF: 0.371 AC: 781 AN: 2104

Alfa AF: 0.376 Hom.: 49025

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

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		-0.94
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: rs2720460; hg19: chr4-104054686;