4-103108588-CTAAA-C

Variant names:

• chr4-103108588-CTAAA-C
• rs142557236
• NM_001813.3:c.8011+211_8011+214delTTTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001813.3(CENPE):​c.8011+211_8011+214delTTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,960 control chromosomes in the GnomAD database, including 2,296 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2296 hom., cov: 28)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.898
• 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: AR, Unknown Classification: LIMITED Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-103108588-CTAAA-C is Benign according to our data. Variant chr4-103108588-CTAAA-C is described in ClinVar as Benign. ClinVar VariationId is 1259061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 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.8011+211_8011+214delTTTA		intron	N/A	NP_001804.2	Q02224-1
	CENPE	NM_001286734.2		c.7648+211_7648+214delTTTA		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.8011+211_8011+214delTTTA		intron	N/A	ENSP00000265148.3	Q02224-1
	CENPE	ENST00000380026.8	TSL:1	c.7648+211_7648+214delTTTA		intron	N/A	ENSP00000369365.3	Q02224-3
	CENPE	ENST00000933323.1		c.8014+211_8014+214delTTTA		intron	N/A	ENSP00000603382.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24461 AN: 151842 Hom.: 2294 Cov.: 28

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.161 AC: 24471 AN: 151960 Hom.: 2296 Cov.: 28 AF XY: 0.164 AC XY: 12181 AN XY: 74234

African (AFR) AF: 0.0665 AC: 2762 AN: 41514

American (AMR) AF: 0.141 AC: 2148 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3470

East Asian (EAS) AF: 0.156 AC: 807 AN: 5168

South Asian (SAS) AF: 0.109 AC: 526 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3203 AN: 10514

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13702 AN: 67902

Other (OTH) AF: 0.167 AC: 353 AN: 2116

Alfa AF: 0.191 Hom.: 382

Bravo AF: 0.148

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
PhyloP100		0.90
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: rs142557236; hg19: chr4-104029745;