rs11250

chr4-67514497-G-Achr4-67514497-G-Cchr4-67514497-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/18 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550

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]

ACMG classification

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	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	c.1021C>T	p.Leu341Phe	missense_variant	8/19	1	NM_001812.4	P1
CENPC	ENST00000510189.5	n.1169C>T		non_coding_transcript_exon_variant	8/14	1
CENPC	ENST00000506882.5	c.1021C>T	p.Leu341Phe	missense_variant, NMD_transcript_variant	8/20	1
CENPC	ENST00000513216.5	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.: 31

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

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.: 50 AF XY: 0.623 AC XY: 452499 AN XY: 726648

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.: 31 AF XY: 0.635 AC XY: 47152 AN XY: 74236

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	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	12
Dann	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.12	T
Sift4G	Benign	0.073	T
Polyphen		0.97	D
Vest4		0.019
MPC		0.083
ClinPred		0.0066	T
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

Other links and lift over

dbSNP: rs11250; hg19: chr4-68380215; COSMIC: COSV56625480; COSMIC: COSV56625480;