rs7683537

Variant names:

• chr4-184710844-T-C
• rs7683537
• NM_024629.4:c.689-664A>G

Variant summary

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

The NM_024629.4(CENPU):​c.689-664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,034 control chromosomes in the GnomAD database, including 2,665 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 (2665 hom., cov: 32)
• Consequence: CENPU NM_024629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPU	NM_024629.4	c.689-664A>G		intron_variant	Intron 7 of 12	ENST00000281453.10	NP_078905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPU	ENST00000281453.10	c.689-664A>G		intron_variant	Intron 7 of 12	1	NM_024629.4	ENSP00000281453.5
CENPU	ENST00000510146.5	n.689-664A>G		intron_variant	Intron 7 of 11	1		ENSP00000423248.1
CENPU	ENST00000506535.1	n.144-438A>G		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26975 AN: 151916 Hom.: 2663 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.178 AC: 27000 AN: 152034 Hom.: 2665 Cov.: 32 AF XY: 0.174 AC XY: 12965 AN XY: 74326

African (AFR) AF: 0.262 AC: 10871 AN: 41420

American (AMR) AF: 0.141 AC: 2152 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.106 AC: 509 AN: 4824

European-Finnish (FIN) AF: 0.147 AC: 1554 AN: 10604

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10701 AN: 67948

Other (OTH) AF: 0.189 AC: 397 AN: 2106

Alfa AF: 0.172 Hom.: 309

Bravo AF: 0.183

Asia WGS AF: 0.0680 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.63
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: rs7683537; hg19: chr4-185631998;