Variant rs11250 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001812.4(CENPC):c.1021C>T(p.Leu341Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,612,834 control chromosomes in the GnomAD database, including 314,991 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.63 ( 30454 hom., cov: 31)

Exomes 𝑓: 0.62 ( 284537 hom. )

Consequence

CENPC
NM_001812.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.550

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1516624E-6).

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/exons	MANE	UniProt
CENPC	NM_001812.4 linkuse as main transcript	c.1021C>T	p.Leu341Phe	missense_variant	8/19	ENST00000273853.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPC	ENST00000273853.11 linkuse as main transcript	c.1021C>T	p.Leu341Phe	missense_variant	8/19	1	NM_001812.4	P1	Q03188-1
CENPC	ENST00000510189.5 linkuse as main transcript	n.1169C>T		non_coding_transcript_exon_variant	8/14	1
CENPC	ENST00000506882.5 linkuse as main transcript	c.1021C>T	p.Leu341Phe	missense_variant, NMD_transcript_variant	8/20	1			Q03188-2
CENPC	ENST00000513216.5 linkuse as main transcript	c.742C>T	p.Leu248Phe	missense_variant, NMD_transcript_variant	4/15	5

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95696

AN:

151836

Hom.:

30407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

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:

0.726

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.669

GnomAD3 exomes

AF:

0.659

AC:

163200

AN:

247758

Hom.:

54658

AF XY:

0.655

AC XY:

88060

AN XY:

134402

show subpopulations

Gnomad AFR exome

AF:

0.628

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.818

Gnomad SAS exome

AF:

0.682

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.622

AC:

908046

AN:

1460880

Hom.:

284537

Cov.:

AF XY:

0.623

AC XY:

452499

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.641

Gnomad4 AMR exome

AF:

0.794

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.680

Gnomad4 FIN exome

AF:

0.571

Gnomad4 NFE exome

AF:

0.604

Gnomad4 OTH exome

AF:

0.641

GnomAD4 genome

AF:

0.630

AC:

95791

AN:

151954

Hom.:

30454

Cov.:

AF XY:

0.635

AC XY:

47152

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.630

Gnomad4 AMR

AF:

0.733

Gnomad4 ASJ

AF:

0.631

Gnomad4 EAS

AF:

0.813

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.672

Alfa

AF:

0.613

Hom.:

13833

Bravo

AF:

0.645

TwinsUK

AF:

0.603

AC:

2236

ALSPAC

AF:

0.609

AC:

2348

ESP6500AA

AF:

0.631

AC:

2383

ESP6500EA

AF:

0.603

AC:

4963

ExAC

AF:

0.653

AC:

78938

Asia WGS

AF:

0.771

AC:

2681

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

REVEL

Benign

0.16

Sift

Benign

0.12

Sift4G

Benign

0.073

Polyphen

0.97

Vest4

0.019

MPC

0.083

ClinPred

0.0066

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.034

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over