rs11895026

Positions:

• chr2-24813989-C-A
• chr2-24813989-C-T

Variant summary

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

The NM_001322101.2(CENPO):​c.217-387C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,088 control chromosomes in the GnomAD database, including 2,655 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 0.18 (2655 hom., cov: 31)
• Consequence: CENPO NM_001322101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPO	NM_001322101.2	c.217-387C>A		intron_variant		ENST00000380834.7	NP_001309030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPO	ENST00000380834.7	c.217-387C>A		intron_variant		5	NM_001322101.2	ENSP00000370214	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26725 AN: 151970 Hom.: 2649 Cov.: 31

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.176 AC: 26757 AN: 152088 Hom.: 2655 Cov.: 31 AF XY: 0.175 AC XY: 13000 AN XY: 74350

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.174

Alfa AF: 0.164 Hom.: 522

Bravo AF: 0.164

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.49

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: rs11895026; hg19: chr2-25036858;