Genetic Variant CENPP:c.564+114378C>T (chr9-92494237-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012267.3(CENPP):c.564+114378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,354,886 control chromosomes in the GnomAD database, including 174,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 15557 hom., cov: 32)

Exomes 𝑓: 0.51 ( 158768 hom. )

Consequence

CENPP
NM_001012267.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

6 publications found

Variant links:

Genes affected

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

CENPP links:

ECM2 (HGNC:3154): (extracellular matrix protein 2) ECM2 encodes extracellular matrix protein 2, so named because it shares extensive similarity with known extracelluar matrix proteins. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ECM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012267.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CENPP	NM_001012267.3	MANE Select	c.564+114378C>T	intron	N/A	NP_001012267.1	Q6IPU0-1
ECM2	NM_001197296.2		c.1866-88G>A	intron	N/A	NP_001184225.1	O94769-2
CENPP	NM_001286969.1		c.228+114378C>T	intron	N/A	NP_001273898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+114378C>T		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	ECM2	ENST00000444490.6	TSL:1	c.1866-88G>A		intron	N/A	ENSP00000393971.2	O94769-2

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62794

AN:

151964

Hom.:

15550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.798

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.506

AC:

608160

AN:

1202804

Hom.:

158768

AF XY:

0.504

AC XY:

303750

AN XY:

602228

show subpopulations

African (AFR)

AF:

0.119

AC:

3398

AN:

28658

American (AMR)

AF:

0.576

AC:

21654

AN:

37596

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

10323

AN:

22320

East Asian (EAS)

AF:

0.757

AC:

27957

AN:

36918

South Asian (SAS)

AF:

0.475

AC:

34021

AN:

71668

European-Finnish (FIN)

AF:

0.549

AC:

19276

AN:

35118

Middle Eastern (MID)

AF:

0.448

AC:

2327

AN:

5196

European-Non Finnish (NFE)

AF:

0.507

AC:

463305

AN:

913760

Other (OTH)

AF:

0.502

AC:

25899

AN:

51570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

13558

27116

40673

54231

67789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12924

25848

38772

51696

64620

<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:

0.413

AC:

62803

AN:

152082

Hom.:

15557

Cov.:

AF XY:

0.420

AC XY:

31191

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.138

AC:

5734

AN:

41498

American (AMR)

AF:

0.510

AC:

7795

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1641

AN:

3468

East Asian (EAS)

AF:

0.798

AC:

4134

AN:

5182

South Asian (SAS)

AF:

0.480

AC:

2313

AN:

4820

European-Finnish (FIN)

AF:

0.539

AC:

5688

AN:

10560

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34225

AN:

67958

Other (OTH)

AF:

0.437

AC:

922

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1676

3353

5029

6706

8382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.475

Hom.:

30539

Bravo

AF:

0.400

Asia WGS

AF:

0.600

AC:

2088

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.2

(source)

DANN

Benign

0.66

PhyloP100

-0.27

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

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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