Genetic Variant CENPC:n.*19A>G (chr4-67510990-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000506882.5(CENPC):n.*19A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 455,750 control chromosomes in the GnomAD database, including 94,518 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 0.63 ( 30445 hom., cov: 32)

Exomes 𝑓: 0.64 ( 64073 hom. )

Consequence

CENPC
ENST00000506882.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

Publications

6 publications found

Variant links:

Genes affected

CENPC (HGNC:1854): (centromere protein C) Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

CENPC links:

Genome browser will be placed here

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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPC	NM_001812.4 link	c.1612+1412A>G		intron_variant	Intron 9 of 18	ENST00000273853.11	NP_001803.2	Q03188-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11 link	c.1612+1412A>G		intron_variant	Intron 9 of 18	1	NM_001812.4	ENSP00000273853.6		Q03188-1

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95690

AN:

151866

Hom.:

30398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.670

GnomAD2 exomes

AF:

0.675

AC:

86475

AN:

128164

AF XY:

0.668

show subpopulations

Gnomad AFR exome

AF:

0.632

Gnomad AMR exome

AF:

0.795

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.660

GnomAD4 exome

AF:

0.645

AC:

195800

AN:

303766

Hom.:

64073

Cov.:

AF XY:

0.646

AC XY:

111648

AN XY:

172954

show subpopulations

African (AFR)

AF:

0.638

AC:

5498

AN:

8618

American (AMR)

AF:

0.795

AC:

21697

AN:

27280

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

6964

AN:

10784

East Asian (EAS)

AF:

0.812

AC:

7474

AN:

9208

South Asian (SAS)

AF:

0.677

AC:

40432

AN:

59684

European-Finnish (FIN)

AF:

0.571

AC:

7064

AN:

12362

Middle Eastern (MID)

AF:

0.732

AC:

2034

AN:

2778

European-Non Finnish (NFE)

AF:

0.601

AC:

95503

AN:

158828

Other (OTH)

AF:

0.642

AC:

9134

AN:

14224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

3791

7583

11374

15166

18957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.630

AC:

95785

AN:

151984

Hom.:

30445

Cov.:

AF XY:

0.635

AC XY:

47170

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.630

AC:

26098

AN:

41440

American (AMR)

AF:

0.733

AC:

11180

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

2186

AN:

3466

East Asian (EAS)

AF:

0.813

AC:

4205

AN:

5174

South Asian (SAS)

AF:

0.698

AC:

3365

AN:

4820

European-Finnish (FIN)

AF:

0.568

AC:

6005

AN:

10572

Middle Eastern (MID)

AF:

0.729

AC:

213

AN:

292

European-Non Finnish (NFE)

AF:

0.598

AC:

40611

AN:

67952

Other (OTH)

AF:

0.673

AC:

1422

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1807

3613

5420

7226

9033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.613

Hom.:

16811

Bravo

AF:

0.645

Asia WGS

AF:

0.771

AC:

2679

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.24

(source)

DANN

Benign

0.39

PhyloP100

-1.9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over