rs2130392

chr4-184718015-G-Achr4-184718015-G-Cchr4-184718015-G-T

Variant summary

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

The NM_024629.4(CENPU):c.321-819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,106 control chromosomes in the GnomAD database, including 25,128 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 0.55 (25128 hom., cov: 33)
• Consequence: CENPU NM_024629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

Genes affected

CENPU (HGNC:21348): (centromere protein U) The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). MLF1IP, or CENPU, is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPU	NM_024629.4	c.321-819C>T		intron_variant		ENST00000281453.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPU	ENST00000281453.10	c.321-819C>T		intron_variant		1	NM_024629.4	P1
CENPU	ENST00000510146.5	c.321-819C>T		intron_variant, NMD_transcript_variant		1
CENPU	ENST00000514781.1	c.234-819C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83759 AN: 151988 Hom.: 25125 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.551 AC: 83774 AN: 152106 Hom.: 25128 Cov.: 33 AF XY: 0.548 AC XY: 40743 AN XY: 74362

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.562

Alfa AF: 0.657 Hom.: 65257

Bravo AF: 0.524

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.46

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: rs2130392; hg19: chr4-185639169;