rs9511504

chr13-24890091-A-G

Variant summary

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

The NM_018451.5(CENPJ):c.3217-691T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,184 control chromosomes in the GnomAD database, including 4,174 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 0.22 (4174 hom., cov: 32)
• Consequence: CENPJ NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.3217-691T>C		intron_variant		ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.3217-691T>C		intron_variant		1	NM_018451.5	P1
CENPJ	ENST00000418179.1	c.461-691T>C		intron_variant		1
CENPJ	ENST00000616936.4	c.3216+2552T>C		intron_variant, NMD_transcript_variant		1
CENPJ	ENST00000545981.6	c.3217-691T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33538 AN: 152066 Hom.: 4177 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0530

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.220 AC: 33520 AN: 152184 Hom.: 4174 Cov.: 32 AF XY: 0.216 AC XY: 16107 AN XY: 74402

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0525

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.222

Alfa AF: 0.265 Hom.: 913

Bravo AF: 0.212

Asia WGS AF: 0.112 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs9511504; hg19: chr13-25464229;