Genetic Variant NM_001812.4:c.2515+84T>C (chr4-67492096-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001812.4(CENPC):c.2515+84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 886,374 control chromosomes in the GnomAD database, including 174,036 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 ( 30198 hom., cov: 31)

Exomes 𝑓: 0.62 ( 143838 hom. )

Consequence

CENPC
NM_001812.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

4 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=-0.76).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CENPC	NM_001812.4	MANE Select	c.2515+84T>C	intron	N/A	NP_001803.2
CENPC	NM_001362481.2		c.2491+84T>C	intron	N/A	NP_001349410.1
CENPC	NR_155754.2		n.2781+84T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CENPC	ENST00000273853.11	TSL:1 MANE Select	c.2515+84T>C	intron	N/A	ENSP00000273853.6
CENPC	ENST00000506882.5	TSL:1	n.*1239+84T>C	intron	N/A	ENSP00000426078.1
CENPC	ENST00000515140.1	TSL:1	n.*167+84T>C	intron	N/A	ENSP00000425255.1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95309

AN:

151860

Hom.:

30152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.622

AC:

456675

AN:

734396

Hom.:

143838

AF XY:

0.624

AC XY:

235386

AN XY:

377326

show subpopulations

African (AFR)

AF:

0.633

AC:

11482

AN:

18138

American (AMR)

AF:

0.786

AC:

22684

AN:

28854

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

11393

AN:

17740

East Asian (EAS)

AF:

0.793

AC:

25109

AN:

31666

South Asian (SAS)

AF:

0.679

AC:

37298

AN:

54914

European-Finnish (FIN)

AF:

0.572

AC:

24654

AN:

43084

Middle Eastern (MID)

AF:

0.697

AC:

1809

AN:

2594

European-Non Finnish (NFE)

AF:

0.597

AC:

299865

AN:

502394

Other (OTH)

AF:

0.639

AC:

22381

AN:

35012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8073

16146

24218

32291

40364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5746

11492

17238

22984

28730

<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:

0.628

AC:

95401

AN:

151978

Hom.:

30198

Cov.:

AF XY:

0.633

AC XY:

46979

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.621

AC:

25747

AN:

41452

American (AMR)

AF:

0.732

AC:

11178

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

2190

AN:

3472

East Asian (EAS)

AF:

0.812

AC:

4199

AN:

5170

South Asian (SAS)

AF:

0.697

AC:

3353

AN:

4810

European-Finnish (FIN)

AF:

0.568

AC:

5988

AN:

10542

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.598

AC:

40621

AN:

67962

Other (OTH)

AF:

0.672

AC:

1414

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1787

3574

5360

7147

8934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.606

Hom.:

4205

Bravo

AF:

0.642

Asia WGS

AF:

0.768

AC:

2671

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.4

(source)

DANN

Benign

0.89

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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