rs187538280

Variant names:

• chr4-103195156-G-A
• rs187538280
• NM_001813.3:c.435C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-103195156-G-A
• chr4-103195156-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001813.3(CENPE):​c.435C>T​(p.Gly145Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,591,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CENPE NM_001813.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.40
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-103195156-G-A is Benign according to our data. Variant chr4-103195156-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 434700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.

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.435C>T	p.Gly145Gly	synonymous	Exon 5 of 49	NP_001804.2	Q02224-1
	CENPE	NM_001286734.2		c.435C>T	p.Gly145Gly	synonymous	Exon 5 of 47	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.435C>T	p.Gly145Gly	synonymous	Exon 5 of 49	ENSP00000265148.3	Q02224-1
	CENPE	ENST00000380026.8	TSL:1	c.435C>T	p.Gly145Gly	synonymous	Exon 5 of 47	ENSP00000369365.3	Q02224-3
	CENPE	ENST00000933323.1		c.435C>T	p.Gly145Gly	synonymous	Exon 5 of 49	ENSP00000603382.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 151904 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000252 AC: 59 AN: 234396 AF XY: 0.000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000731

Gnomad OTH exome AF: 0.000529

GnomAD4 exome AF: 0.000128 AC: 185 AN: 1439808 Hom.: 0 Cov.: 28 AF XY: 0.000113 AC XY: 81 AN XY: 716382

African (AFR) AF: 0.0000310 AC: 1 AN: 32236

American (AMR) AF: 0.00176 AC: 69 AN: 39134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 38674

South Asian (SAS) AF: 0.00 AC: 0 AN: 81372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 0.0000914 AC: 101 AN: 1104620

Other (OTH) AF: 0.000236 AC: 14 AN: 59378

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41534

American (AMR) AF: 0.00222 AC: 34 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67836

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.000457

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	CENPE-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.0
DANN	Benign	0.68
PhyloP100		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs187538280; hg19: chr4-104116313;