rs355477

Positions:

• chr4-67530807-G-C
• chr4-67530807-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.331+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,478,304 control chromosomes in the GnomAD database, including 284,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (30789 hom., cov: 32)
  • Exomes 𝑓: 0.62 (253956 hom.)
• Consequence: CENPC NM_001812.4 splice_region, intron
• Scores: Splicing: ADA: 0.0006775
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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=-0.83).
• 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.331+8C>G		splice_region_variant, intron_variant		ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11	c.331+8C>G		splice_region_variant, intron_variant		1	NM_001812.4	ENSP00000273853.6
CENPC	ENST00000506882.5	n.331+8C>G		splice_region_variant, intron_variant		1		ENSP00000426078.1
CENPC	ENST00000510189.5	n.479+8C>G		splice_region_variant, intron_variant		1
CENPC	ENST00000513216.5	n.52+8C>G		splice_region_variant, intron_variant		5		ENSP00000421234.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96239 AN: 151844 Hom.: 30743 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.671

GnomAD3 exomes AF: 0.639 AC: 133129 AN: 208350 Hom.: 43272 AF XY: 0.634 AC XY: 71586 AN XY: 112856

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.639

Gnomad EAS exome AF: 0.809

Gnomad SAS exome AF: 0.663

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.616 AC: 816423 AN: 1326346 Hom.: 253956 Cov.: 18 AF XY: 0.617 AC XY: 409231 AN XY: 663766

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.636

GnomAD4 genome AF: 0.634 AC: 96333 AN: 151958 Hom.: 30789 Cov.: 32 AF XY: 0.639 AC XY: 47453 AN XY: 74256

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.674

Alfa AF: 0.584 Hom.: 7137

Bravo AF: 0.649

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00068
dbscSNV1_RF	Benign	0.014
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: rs355477; hg19: chr4-68396525; COSMIC: COSV56625490;