chr4-67513406-T-C

Position:

• chr4-67513406-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.1444+668A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,050 control chromosomes in the GnomAD database, including 30,467 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 (30467 hom., cov: 32)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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=-0.91).
• 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.1444+668A>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.1444+668A>G		intron_variant		1	NM_001812.4	ENSP00000273853.6

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95735 AN: 151932 Hom.: 30420 Cov.: 32

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: 0.729

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.668

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.630 AC: 95830 AN: 152050 Hom.: 30467 Cov.: 32 AF XY: 0.635 AC XY: 47205 AN XY: 74332

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: 0.671

Alfa AF: 0.608 Hom.: 4086

Bravo AF: 0.645

Asia WGS AF: 0.771 AC: 2678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.52

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: rs355464; hg19: chr4-68379124;