rs35213472

Positions:

• chr2-24795640-T-C

Variant summary

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

The NM_001322101.2(CENPO):​c.46+1675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 152,280 control chromosomes in the GnomAD database, including 83 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 0.030 (83 hom., cov: 32)
• Consequence: CENPO NM_001322101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

CENPO (HGNC:28152): (centromere protein O) This gene encodes a component of the interphase centromere complex. The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

CENPO (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPO	NM_001322101.2	c.46+1675T>C		intron_variant		ENST00000380834.7	NP_001309030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPO	ENST00000380834.7	c.46+1675T>C		intron_variant		5	NM_001322101.2	ENSP00000370214.2

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4508 AN: 152162 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0296 AC: 4512 AN: 152280 Hom.: 83 Cov.: 32 AF XY: 0.0315 AC XY: 2343 AN XY: 74448

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0433

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.0516

Gnomad4 FIN AF: 0.0402

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0262 Hom.: 9

Bravo AF: 0.0289

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.32

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: rs35213472; hg19: chr2-25018509;