rs3742165

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_018451.5(CPAP):c.3042A>G(p.Glu1014Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,610,908 control chromosomes in the GnomAD database, including 236,901 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18933 hom., cov: 29)

Exomes 𝑓: 0.54 ( 217968 hom. )

Consequence

CPAP
NM_018451.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.210

Publications

19 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: G2P, Labcorp Genetics (formerly Invitae)
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

new If you want to explore the variant's impact on the transcript NM_018451.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 13-24892817-T-C is Benign according to our data. Variant chr13-24892817-T-C is described in ClinVar as Benign. ClinVar VariationId is 158207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 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.3042A>G	p.Glu1014Glu	synonymous	Exon 10 of 17	NP_060921.3
CPAP	NR_047594.2		n.3209A>G		non_coding_transcript_exon	Exon 10 of 18
CPAP	NR_047595.2		n.3209A>G		non_coding_transcript_exon	Exon 10 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPAP	ENST00000381884.9	TSL:1 MANE Select	c.3042A>G	p.Glu1014Glu	synonymous	Exon 10 of 17	ENSP00000371308.4	Q9HC77-1
CPAP	ENST00000418179.1	TSL:1	c.285A>G	p.Glu95Glu	synonymous	Exon 3 of 4	ENSP00000399334.1	H0Y5L8
CPAP	ENST00000616936.4	TSL:1	n.3042A>G		non_coding_transcript_exon	Exon 10 of 16	ENSP00000477511.1	Q9HC77-2

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73107

AN:

151358

Hom.:

18914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.485

GnomAD2 exomes

AF:

0.549

AC:

137988

AN:

251456

AF XY:

0.544

show subpopulations

Gnomad AFR exome

AF:

0.284

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.712

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.543

AC:

792195

AN:

1459432

Hom.:

217968

Cov.:

AF XY:

0.541

AC XY:

393000

AN XY:

726172

show subpopulations

African (AFR)

AF:

0.285

AC:

9544

AN:

33434

American (AMR)

AF:

0.639

AC:

28573

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

13078

AN:

26118

East Asian (EAS)

AF:

0.712

AC:

28266

AN:

39690

South Asian (SAS)

AF:

0.496

AC:

42748

AN:

86200

European-Finnish (FIN)

AF:

0.618

AC:

33030

AN:

53414

Middle Eastern (MID)

AF:

0.476

AC:

2744

AN:

5764

European-Non Finnish (NFE)

AF:

0.543

AC:

602300

AN:

1109776

Other (OTH)

AF:

0.529

AC:

31912

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

17470

34939

52409

69878

87348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17100

34200

51300

68400

85500

<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:

0.483

AC:

73158

AN:

151476

Hom.:

18933

Cov.:

AF XY:

0.490

AC XY:

36199

AN XY:

73950

show subpopulations

African (AFR)

AF:

0.297

AC:

12239

AN:

41276

American (AMR)

AF:

0.580

AC:

8832

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1762

AN:

3470

East Asian (EAS)

AF:

0.718

AC:

3699

AN:

5154

South Asian (SAS)

AF:

0.490

AC:

2344

AN:

4784

European-Finnish (FIN)

AF:

0.632

AC:

6576

AN:

10398

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.534

AC:

36272

AN:

67874

Other (OTH)

AF:

0.482

AC:

1012

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1761

3522

5282

7043

8804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.505

Hom.:

30511

Bravo

AF:

0.473

Asia WGS

AF:

0.559

AC:

1937

AN:

3476

EpiCase

AF:

0.520

EpiControl

AF:

0.528

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (4)

Microcephaly 6, primary, autosomal recessive (2)

Seckel syndrome 4 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.0

(source)

DANN

Benign

0.64

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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