rs1029113

chr13-24916255-C-G

Variant summary

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

The NM_018451.5(CENPJ):c.-66-3164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,002 control chromosomes in the GnomAD database, including 27,814 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 0.59 (27814 hom., cov: 31)
• Consequence: CENPJ NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

CENPJ (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.-66-3164G>C		intron_variant		ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.-66-3164G>C		intron_variant		1	NM_018451.5	P1
CENPJ	ENST00000616936.4	c.-66-3164G>C		intron_variant, NMD_transcript_variant		1
CENPJ	ENST00000545981.6	c.-66-3164G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89761 AN: 151884 Hom.: 27793 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.591 AC: 89815 AN: 152002 Hom.: 27814 Cov.: 31 AF XY: 0.595 AC XY: 44196 AN XY: 74306

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.576

Alfa AF: 0.619 Hom.: 3741

Bravo AF: 0.580

Asia WGS AF: 0.601 AC: 2087 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	0.28
Dann	Benign	0.57

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: rs1029113; hg19: chr13-25490393;