rs2278483

Variant names:

• chr2-24817213-C-T
• rs2278483
• NM_001322101.2:c.766+396C>T

Variant summary

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

The NM_001322101.2(CENPO):​c.766+396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,130 control chromosomes in the GnomAD database, including 3,533 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 0.21 (3533 hom., cov: 31)
• Consequence: CENPO NM_001322101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 18 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPO	NM_001322101.2	c.766+396C>T		intron_variant	Intron 6 of 7	ENST00000380834.7	NP_001309030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPO	ENST00000380834.7	c.766+396C>T		intron_variant	Intron 6 of 7	5	NM_001322101.2	ENSP00000370214.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32351 AN: 152012 Hom.: 3517 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.213 AC: 32406 AN: 152130 Hom.: 3533 Cov.: 31 AF XY: 0.210 AC XY: 15599 AN XY: 74350

African (AFR) AF: 0.222 AC: 9200 AN: 41478

American (AMR) AF: 0.146 AC: 2235 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3470

East Asian (EAS) AF: 0.119 AC: 618 AN: 5180

South Asian (SAS) AF: 0.108 AC: 520 AN: 4826

European-Finnish (FIN) AF: 0.257 AC: 2714 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15468 AN: 67992

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.221 Hom.: 12591

Bravo AF: 0.207

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.42
PhyloP100		1.1
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: rs2278483; hg19: chr2-25040082;