chr4-103106487-G-A

Variant names:

• chr4-103106487-G-A
• rs17215862
• NM_001813.3:c.8012-171C>T

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.8012-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,132 control chromosomes in the GnomAD database, including 2,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2311 hom., cov: 32)
• Consequence: CENPE NM_001813.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.976
• 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: AR, Unknown Classification: LIMITED Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-103106487-G-A is Benign according to our data. Variant chr4-103106487-G-A is described in ClinVar as Benign. ClinVar VariationId is 1290610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 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.8012-171C>T		intron	N/A	NP_001804.2	Q02224-1
	CENPE	NM_001286734.2		c.7649-171C>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.8012-171C>T		intron	N/A	ENSP00000265148.3	Q02224-1
	CENPE	ENST00000380026.8	TSL:1	c.7649-171C>T		intron	N/A	ENSP00000369365.3	Q02224-3
	CENPE	ENST00000933323.1		c.8015-171C>T		intron	N/A	ENSP00000603382.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25617 AN: 152012 Hom.: 2312 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.169 AC: 25641 AN: 152132 Hom.: 2311 Cov.: 32 AF XY: 0.170 AC XY: 12677 AN XY: 74372

African (AFR) AF: 0.131 AC: 5429 AN: 41506

American (AMR) AF: 0.209 AC: 3189 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.140 AC: 727 AN: 5180

South Asian (SAS) AF: 0.306 AC: 1476 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10586

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12189 AN: 67982

Other (OTH) AF: 0.180 AC: 380 AN: 2114

Alfa AF: 0.176 Hom.: 808

Bravo AF: 0.168

Asia WGS AF: 0.230 AC: 800 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
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		0.98
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: rs17215862; hg19: chr4-104027644;