Genetic Variant CENPC:c.*2352A>G (chr4-67470253-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 NM_001812.4(CENPC):c.*2352A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,944 control chromosomes in the GnomAD database, including 29,946 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 ( 29918 hom., cov: 30)

Exomes 𝑓: 0.62 ( 28 hom. )

Consequence

CENPC
NM_001812.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Publications

1 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=-0.96).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CENPC	NM_001812.4 link	c.*2352A>G	3_prime_UTR_variant	Exon 19 of 19	ENST00000273853.11	NP_001803.2
CENPC	NR_155754.2 link	n.5450A>G	non_coding_transcript_exon_variant	Exon 19 of 19
CENPC	NM_001362481.2 link	c.*2352A>G	3_prime_UTR_variant	Exon 19 of 19		NP_001349410.1
CENPC	XM_047449526.1 link	c.*2360A>G	3_prime_UTR_variant	Exon 18 of 18		XP_047305482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11 link	c.*2352A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_001812.4	ENSP00000273853.6

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94840

AN:

151666

Hom.:

29877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.632

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.596

Gnomad OTH

AF:

0.663

GnomAD4 exome

AF:

0.619

AC:

AN:

160

Hom.:

Cov.:

AF XY:

0.612

AC XY:

AN XY:

116

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.612

AC:

AN:

134

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.625

AC:

94929

AN:

151784

Hom.:

29918

Cov.:

AF XY:

0.630

AC XY:

46741

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.615

AC:

25431

AN:

41362

American (AMR)

AF:

0.732

AC:

11161

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

2191

AN:

3466

East Asian (EAS)

AF:

0.812

AC:

4183

AN:

5150

South Asian (SAS)

AF:

0.697

AC:

3349

AN:

4806

European-Finnish (FIN)

AF:

0.569

AC:

5977

AN:

10512

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.596

AC:

40519

AN:

67932

Other (OTH)

AF:

0.666

AC:

1405

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1761

3522

5283

7044

8805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.502

Hom.:

1817

Bravo

AF:

0.640

Asia WGS

AF:

0.768

AC:

2670

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.9

(source)

DANN

Benign

0.54

PhyloP100

0.012

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over