NM_018451.5:c.1881G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018451.5(CPAP):​c.1881G>A​(p.Pro627Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,613,606 control chromosomes in the GnomAD database, including 1,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 199 hom., cov: 33)
Exomes 𝑓: 0.010 ( 1264 hom. )

Consequence

CPAP
NM_018451.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.98

Publications

5 publications found
Variant links:
Genes affected
CPAP (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]
CPAP Gene-Disease associations (from GenCC):
  • microcephaly 6 with or without short stature
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • microcephaly 6, primary, autosomal recessive
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • autosomal recessive primary microcephaly
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Seckel syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 13-24906157-C-T is Benign according to our data. Variant chr13-24906157-C-T is described in ClinVar as [Benign]. Clinvar id is 95909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.98 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPAPNM_018451.5 linkc.1881G>A p.Pro627Pro synonymous_variant Exon 7 of 17 ENST00000381884.9 NP_060921.3 Q9HC77-1A8K8P1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPJENST00000381884.9 linkc.1881G>A p.Pro627Pro synonymous_variant Exon 7 of 17 1 NM_018451.5 ENSP00000371308.4 Q9HC77-1
CENPJENST00000616936.4 linkn.1881G>A non_coding_transcript_exon_variant Exon 7 of 16 1 ENSP00000477511.1 Q9HC77-2
CENPJENST00000545981.6 linkn.1881G>A non_coding_transcript_exon_variant Exon 7 of 18 2 ENSP00000441090.2 F6VUX8

Frequencies

GnomAD3 genomes
AF:
0.0181
AC:
2748
AN:
152080
Hom.:
194
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00312
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.132
Gnomad ASJ
AF:
0.0110
Gnomad EAS
AF:
0.0864
Gnomad SAS
AF:
0.00602
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.000779
Gnomad OTH
AF:
0.0163
GnomAD2 exomes
AF:
0.0371
AC:
9325
AN:
251226
AF XY:
0.0291
show subpopulations
Gnomad AFR exome
AF:
0.00234
Gnomad AMR exome
AF:
0.215
Gnomad ASJ exome
AF:
0.00914
Gnomad EAS exome
AF:
0.0774
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000792
Gnomad OTH exome
AF:
0.0261
GnomAD4 exome
AF:
0.0100
AC:
14645
AN:
1461408
Hom.:
1264
Cov.:
34
AF XY:
0.00897
AC XY:
6517
AN XY:
726900
show subpopulations
African (AFR)
AF:
0.00158
AC:
53
AN:
33474
American (AMR)
AF:
0.201
AC:
8970
AN:
44692
Ashkenazi Jewish (ASJ)
AF:
0.00919
AC:
240
AN:
26118
East Asian (EAS)
AF:
0.0968
AC:
3843
AN:
39684
South Asian (SAS)
AF:
0.00316
AC:
272
AN:
86202
European-Finnish (FIN)
AF:
0.0000749
AC:
4
AN:
53412
Middle Eastern (MID)
AF:
0.00260
AC:
15
AN:
5768
European-Non Finnish (NFE)
AF:
0.000575
AC:
639
AN:
1111682
Other (OTH)
AF:
0.0101
AC:
609
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
784
1568
2353
3137
3921
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
194
388
582
776
970
<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:
0.0181
AC:
2761
AN:
152198
Hom.:
199
Cov.:
33
AF XY:
0.0217
AC XY:
1614
AN XY:
74412
show subpopulations
African (AFR)
AF:
0.00311
AC:
129
AN:
41532
American (AMR)
AF:
0.133
AC:
2028
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.0110
AC:
38
AN:
3468
East Asian (EAS)
AF:
0.0865
AC:
448
AN:
5182
South Asian (SAS)
AF:
0.00602
AC:
29
AN:
4814
European-Finnish (FIN)
AF:
0.0000943
AC:
1
AN:
10602
Middle Eastern (MID)
AF:
0.00342
AC:
1
AN:
292
European-Non Finnish (NFE)
AF:
0.000779
AC:
53
AN:
68008
Other (OTH)
AF:
0.0161
AC:
34
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
119
239
358
478
597
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
26
52
78
104
130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00665
Hom.:
34
Bravo
AF:
0.0277
Asia WGS
AF:
0.0420
AC:
145
AN:
3478
EpiCase
AF:
0.00109
EpiControl
AF:
0.00101

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:2
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 23, 2015
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Seckel syndrome 4 Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Microcephaly 6, primary, autosomal recessive Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.46
DANN
Benign
0.35
PhyloP100
-3.0
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

Publications

Other links and lift over

dbSNP: rs75985315; hg19: chr13-25480295; COSMIC: COSV67882944; COSMIC: COSV67882944; API