rs355464

Variant names:

• chr4-67513406-T-C
• rs355464
• NM_001812.4:c.1444+668A>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.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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	NM_001812.4	MANE Select	c.1444+668A>G		intron	N/A	NP_001803.2	Q03188-1
	CENPC	NM_001362481.2		c.1444+668A>G		intron	N/A	NP_001349410.1
	CENPC	NR_155754.2		n.1592+668A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	ENST00000273853.11	TSL:1 MANE Select	c.1444+668A>G		intron	N/A	ENSP00000273853.6	Q03188-1
	CENPC	ENST00000506882.5	TSL:1	n.1444+668A>G		intron	N/A	ENSP00000426078.1	Q03188-2
	CENPC	ENST00000510189.5	TSL:1	n.1592+668A>G		intron	N/A

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

African (AFR) AF: 0.630 AC: 26116 AN: 41456

American (AMR) AF: 0.733 AC: 11187 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4206 AN: 5174

South Asian (SAS) AF: 0.698 AC: 3366 AN: 4824

European-Finnish (FIN) AF: 0.568 AC: 6010 AN: 10582

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.598 AC: 40628 AN: 67972

Other (OTH) AF: 0.671 AC: 1416 AN: 2110

Alfa AF: 0.608 Hom.: 4235

Bravo AF: 0.645

Asia WGS AF: 0.771 AC: 2678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.52
PhyloP100		-0.44
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: rs355464; hg19: chr4-68379124;