rs1497430

chr4-67492096-A-Gchr4-67492096-A-T

Variant summary

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

The NM_001812.4(CENPC):c.2515+84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 886,374 control chromosomes in the GnomAD database, including 174,036 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 (30198 hom., cov: 31)
  • Exomes 𝑓: 0.62 (143838 hom.)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 (BayesDel_noAF=-0.76).
• 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.2515+84T>C		intron_variant		ENST00000273853.11
CENPC	NM_001362481.2	c.2491+84T>C		intron_variant
CENPC	XM_047449526.1	c.2515+84T>C		intron_variant
CENPC	NR_155754.2	n.2781+84T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPC	ENST00000273853.11	c.2515+84T>C		intron_variant		1	NM_001812.4	P1
CENPC	ENST00000506882.5	c.*1239+84T>C		intron_variant, NMD_transcript_variant		1
CENPC	ENST00000515140.1	c.*167+84T>C		intron_variant, NMD_transcript_variant		1
CENPC	ENST00000513216.5	c.*167+84T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95309 AN: 151860 Hom.: 30152 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.622 AC: 456675 AN: 734396 Hom.: 143838 AF XY: 0.624 AC XY: 235386 AN XY: 377326

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.628 AC: 95401 AN: 151978 Hom.: 30198 Cov.: 31 AF XY: 0.633 AC XY: 46979 AN XY: 74262

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.732

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: 0.672

Alfa AF: 0.606 Hom.: 4061

Bravo AF: 0.642

Asia WGS AF: 0.768 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.4
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1497430; hg19: chr4-68357814;