chr4-67520364-T-C

Variant names:

• chr4-67520364-T-C
• rs355506
• NM_001812.4:c.332-862A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001812.4(CENPC):​c.332-862A>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 151,952 control chromosomes in the GnomAD database, including 30,452 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 (30452 hom., cov: 31)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	NM_001812.4	MANE Select	c.332-862A>G		intron	N/A	NP_001803.2
	CENPC	NM_001362481.2		c.332-862A>G		intron	N/A	NP_001349410.1
	CENPC	NR_155754.2		n.480-862A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	ENST00000273853.11	TSL:1 MANE Select	c.332-862A>G		intron	N/A	ENSP00000273853.6
	CENPC	ENST00000506882.5	TSL:1	n.332-862A>G		intron	N/A	ENSP00000426078.1
	CENPC	ENST00000510189.5	TSL:1	n.480-862A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95699 AN: 151834 Hom.: 30405 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.630 AC: 95794 AN: 151952 Hom.: 30452 Cov.: 31 AF XY: 0.635 AC XY: 47172 AN XY: 74266

African (AFR) AF: 0.630 AC: 26091 AN: 41410

American (AMR) AF: 0.733 AC: 11207 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4190 AN: 5160

South Asian (SAS) AF: 0.698 AC: 3356 AN: 4806

European-Finnish (FIN) AF: 0.569 AC: 6008 AN: 10564

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40616 AN: 67940

Other (OTH) AF: 0.673 AC: 1419 AN: 2110

Alfa AF: 0.627 Hom.: 9300

Bravo AF: 0.645

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs355506; hg19: chr4-68386082;