chr2-24794839-G-C

Variant names:

• chr2-24794839-G-C
• rs41523444
• NM_001322101.2:c.46+874G>C

Variant summary

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

The NM_001322101.2(CENPO):​c.46+874G>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 152,228 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: 33)
• Consequence: CENPO NM_001322101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPO	NM_001322101.2	c.46+874G>C		intron_variant	Intron 2 of 7	ENST00000380834.7	NP_001309030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPO	ENST00000380834.7	c.46+874G>C		intron_variant	Intron 2 of 7	5	NM_001322101.2	ENSP00000370214.2

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4505 AN: 152110 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0661

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0401

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0234

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: 4509 AN: 152228 Hom.: 83 Cov.: 33 AF XY: 0.0315 AC XY: 2343 AN XY: 74424

African (AFR) AF: 0.0258 AC: 1073 AN: 41530

American (AMR) AF: 0.0431 AC: 659 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.0660 AC: 342 AN: 5180

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4826

European-Finnish (FIN) AF: 0.0401 AC: 425 AN: 10590

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0234 AC: 1590 AN: 68026

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0260 Hom.: 9

Bravo AF: 0.0289

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		0.081
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs41523444; hg19: chr2-25017708;