Genetic Variant CPAP:p.Pro627Pro (chr13-24906157-C-T) – ACMG Classification: Benign (-21 pts)

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

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

CPAP links:

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CPAP	NM_018451.5	MANE Select	c.1881G>A	p.Pro627Pro	synonymous	Exon 7 of 17	NP_060921.3
CPAP	NR_047594.2		n.2048G>A		non_coding_transcript_exon	Exon 7 of 18
CPAP	NR_047595.2		n.2048G>A		non_coding_transcript_exon	Exon 7 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPAP	ENST00000381884.9	TSL:1 MANE Select	c.1881G>A	p.Pro627Pro	synonymous	Exon 7 of 17	ENSP00000371308.4	Q9HC77-1
CPAP	ENST00000616936.4	TSL:1	n.1881G>A		non_coding_transcript_exon	Exon 7 of 16	ENSP00000477511.1	Q9HC77-2
CPAP	ENST00000926443.1		c.1881G>A	p.Pro627Pro	synonymous	Exon 7 of 18	ENSP00000596502.1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2748

AN:

152080

Hom.:

194

Cov.:

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.:

AF XY:

0.00897

AC XY:

6517

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.00158

AC:

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:

AN:

53412

Middle Eastern (MID)

AF:

0.00260

AC:

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

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

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.:

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:

AN:

3468

East Asian (EAS)

AF:

0.0865

AC:

448

AN:

5182

South Asian (SAS)

AF:

0.00602

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68008

Other (OTH)

AF:

0.0161

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

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

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.:

Bravo

AF:

0.0277

Asia WGS

AF:

0.0420

AC:

145

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00101

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Microcephaly 6, primary, autosomal recessive (1)

Seckel syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.46

(source)

DANN

Benign

0.35

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over