rs148582447

Variant names:

• chr4-103110950-G-A
• rs148582447
• NM_001813.3:c.7602C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-103110950-G-A
• chr4-103110950-G-C
• chr4-103110950-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001813.3(CENPE):​c.7602C>T​(p.Ser2534Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,610,262 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: CENPE NM_001813.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.81
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-103110950-G-A is Benign according to our data. Variant chr4-103110950-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.7602C>T	p.Ser2534Ser	synonymous	Exon 47 of 49	NP_001804.2	Q02224-1
	CENPE	NM_001286734.2		c.7239C>T	p.Ser2413Ser	synonymous	Exon 45 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.7602C>T	p.Ser2534Ser	synonymous	Exon 47 of 49	ENSP00000265148.3	Q02224-1
	CENPE	ENST00000380026.8	TSL:1	c.7239C>T	p.Ser2413Ser	synonymous	Exon 45 of 47	ENSP00000369365.3	Q02224-3
	CENPE	ENST00000933323.1		c.7605C>T	p.Ser2535Ser	synonymous	Exon 47 of 49	ENSP00000603382.1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 241 AN: 151960 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00194 AC: 482 AN: 249092 AF XY: 0.00195

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00133 AC: 1935 AN: 1458184 Hom.: 5 Cov.: 30 AF XY: 0.00137 AC XY: 997 AN XY: 725436

African (AFR) AF: 0.000960 AC: 32 AN: 33322

American (AMR) AF: 0.00225 AC: 100 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 275 AN: 25976

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39532

South Asian (SAS) AF: 0.00167 AC: 143 AN: 85670

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53344

Middle Eastern (MID) AF: 0.00713 AC: 41 AN: 5754

European-Non Finnish (NFE) AF: 0.00108 AC: 1203 AN: 1109952

Other (OTH) AF: 0.00213 AC: 128 AN: 60216

GnomAD4 genome AF: 0.00158 AC: 240 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74348

African (AFR) AF: 0.00106 AC: 44 AN: 41486

American (AMR) AF: 0.00308 AC: 47 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 67990

Other (OTH) AF: 0.00474 AC: 10 AN: 2108

Alfa AF: 0.00216 Hom.: 1

Bravo AF: 0.00182

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.49
PhyloP100		-1.8
Mutation Taster		=93/7	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: rs148582447; hg19: chr4-104032107;