rs2130392

Variant names:

• chr4-184718015-G-A
• rs2130392
• NM_024629.4:c.321-819C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-184718015-G-A
• chr4-184718015-G-C
• chr4-184718015-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPU	NM_024629.4	MANE Select	c.321-819C>T		intron	N/A	NP_078905.2
	CENPU	NR_104593.2		n.355-819C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPU	ENST00000281453.10	TSL:1 MANE Select	c.321-819C>T		intron	N/A	ENSP00000281453.5	Q71F23-1
	CENPU	ENST00000510146.5	TSL:1	n.321-819C>T		intron	N/A	ENSP00000423248.1	Q09GN1
	CENPU	ENST00000950880.1		c.321-819C>T		intron	N/A	ENSP00000620939.1

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

African (AFR) AF: 0.330 AC: 13699 AN: 41490

American (AMR) AF: 0.493 AC: 7536 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2375 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1493 AN: 5168

South Asian (SAS) AF: 0.565 AC: 2721 AN: 4816

European-Finnish (FIN) AF: 0.701 AC: 7419 AN: 10588

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46580 AN: 67974

Other (OTH) AF: 0.562 AC: 1190 AN: 2116

Alfa AF: 0.646 Hom.: 133122

Bravo AF: 0.524

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		-0.45
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: rs2130392; hg19: chr4-185639169;