4-67510990-T-C

Position:

• chr4-67510990-T-C

Variant summary

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

The NM_001812.4(CENPC):​c.1612+1412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 455,750 control chromosomes in the GnomAD database, including 94,518 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 (30445 hom., cov: 32)
  • Exomes 𝑓: 0.64 (64073 hom.)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• 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	Protein	UniProt
CENPC	NM_001812.4	c.1612+1412A>G		intron_variant		ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11	c.1612+1412A>G		intron_variant		1	NM_001812.4	ENSP00000273853.6

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95690 AN: 151866 Hom.: 30398 Cov.: 32

Gnomad AFR AF: 0.629

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: 0.732

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.670

GnomAD3 exomes AF: 0.675 AC: 86475 AN: 128164 Hom.: 29731 AF XY: 0.668 AC XY: 46927 AN XY: 70206

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.819

Gnomad SAS exome AF: 0.679

Gnomad FIN exome AF: 0.566

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.660

GnomAD4 exome AF: 0.645 AC: 195800 AN: 303766 Hom.: 64073 Cov.: 0 AF XY: 0.646 AC XY: 111648 AN XY: 172954

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.642

GnomAD4 genome AF: 0.630 AC: 95785 AN: 151984 Hom.: 30445 Cov.: 32 AF XY: 0.635 AC XY: 47170 AN XY: 74286

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: 0.673

Alfa AF: 0.613 Hom.: 15226

Bravo AF: 0.645

Asia WGS AF: 0.771 AC: 2679 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.39

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: rs190255; hg19: chr4-68376708;