rs1056787

Variant names:

• chr4-67514352-C-T
• rs1056787
• NM_001812.4:c.1166G>A

Variant summary

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

The NM_001812.4(CENPC):​c.1166G>A​(p.Gly389Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 1,612,198 control chromosomes in the GnomAD database, including 5,776 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.057 (329 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5447 hom.)
• Consequence: CENPC NM_001812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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=0.002503246).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPC	NM_001812.4	c.1166G>A	p.Gly389Asp	missense_variant	Exon 8 of 19	ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11	c.1166G>A	p.Gly389Asp	missense_variant	Exon 8 of 19	1	NM_001812.4	ENSP00000273853.6

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8606 AN: 152068 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.0550

GnomAD3 exomes AF: 0.0579 AC: 14329 AN: 247656 Hom.: 518 AF XY: 0.0579 AC XY: 7779 AN XY: 134354

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.0374

Gnomad ASJ exome AF: 0.0490

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0114

Gnomad FIN exome AF: 0.0543

Gnomad NFE exome AF: 0.0930

Gnomad OTH exome AF: 0.0665

GnomAD4 exome AF: 0.0812 AC: 118532 AN: 1460012 Hom.: 5447 Cov.: 31 AF XY: 0.0790 AC XY: 57400 AN XY: 726340

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.0378

Gnomad4 ASJ exome AF: 0.0506

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.0543

Gnomad4 NFE exome AF: 0.0959

Gnomad4 OTH exome AF: 0.0715

GnomAD4 genome AF: 0.0565 AC: 8601 AN: 152186 Hom.: 329 Cov.: 32 AF XY: 0.0538 AC XY: 3999 AN XY: 74394

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0807 Hom.: 1023

Bravo AF: 0.0556

TwinsUK AF: 0.0987 AC: 366

ALSPAC AF: 0.108 AC: 415

ESP6500AA AF: 0.0182 AC: 66

ESP6500EA AF: 0.0903 AC: 737

ExAC AF: 0.0595 AC: 7183

Asia WGS AF: 0.00982 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.6
DANN	Benign	0.37
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.045
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.050
ClinPred		0.0014	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.019

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: rs1056787; hg19: chr4-68380070;