rs61751594

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001813.3(CENPE):​c.4791A>G​(p.Arg1597Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,048 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CENPE
NM_001813.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

Publications

5 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 4-103145116-T-C is Benign according to our data. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-103145116-T-C is described in CliVar as Likely_benign. Clinvar id is 721739.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENPENM_001813.3 linkc.4791A>G p.Arg1597Arg synonymous_variant Exon 32 of 49 ENST00000265148.9 NP_001804.2 Q02224-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPEENST00000265148.9 linkc.4791A>G p.Arg1597Arg synonymous_variant Exon 32 of 49 2 NM_001813.3 ENSP00000265148.3 Q02224-1
CENPEENST00000380026.8 linkc.4716A>G p.Arg1572Arg synonymous_variant Exon 31 of 47 1 ENSP00000369365.3 Q02224-3
CENPEENST00000515478.1 linkn.*187A>G downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1458906
Hom.:
0
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
725724
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33286
American (AMR)
AF:
0.00
AC:
0
AN:
44386
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26046
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39616
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85590
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53180
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
0.0000153
AC:
17
AN:
1110820
Other (OTH)
AF:
0.00
AC:
0
AN:
60228
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.466
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74318
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41444
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68008
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
9

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 31, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.2
DANN
Benign
0.65
PhyloP100
-1.1

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

Publications

Other links and lift over

dbSNP: rs61751594; hg19: chr4-104066273; API