rs188991038

Variant names:

• chr4-103110812-T-C
• rs188991038
• NM_001813.3:c.7724+16A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001813.3(CENPE):​c.7724+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000884 in 1,562,166 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (3 hom.)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.46
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-103110812-T-C is Benign according to our data. Variant chr4-103110812-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1301481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

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.7724+16A>G		intron	N/A	NP_001804.2	Q02224-1
	CENPE	NM_001286734.2		c.7361+16A>G		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.7724+16A>G		intron	N/A	ENSP00000265148.3	Q02224-1
	CENPE	ENST00000380026.8	TSL:1	c.7361+16A>G		intron	N/A	ENSP00000369365.3	Q02224-3
	CENPE	ENST00000933323.1		c.7727+16A>G		intron	N/A	ENSP00000603382.1

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 583 AN: 152236 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00118 AC: 256 AN: 217240 AF XY: 0.000900

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000644

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000385

GnomAD4 exome AF: 0.000562 AC: 792 AN: 1409812 Hom.: 3 Cov.: 26 AF XY: 0.000539 AC XY: 377 AN XY: 700028

African (AFR) AF: 0.0115 AC: 361 AN: 31388

American (AMR) AF: 0.000683 AC: 26 AN: 38072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23514

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39102

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 77884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51740

Middle Eastern (MID) AF: 0.00130 AC: 6 AN: 4630

European-Non Finnish (NFE) AF: 0.000305 AC: 331 AN: 1085278

Other (OTH) AF: 0.00113 AC: 66 AN: 58204

GnomAD4 genome AF: 0.00387 AC: 589 AN: 152354 Hom.: 1 Cov.: 32 AF XY: 0.00369 AC XY: 275 AN XY: 74504

African (AFR) AF: 0.0129 AC: 536 AN: 41582

American (AMR) AF: 0.00209 AC: 32 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00214 Hom.: 0

Bravo AF: 0.00391

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.48
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

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: rs188991038; hg19: chr4-104031969;