rs12871627

Positions:

• chr13-24904650-G-C

Variant summary

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

The NM_018451.5(CENPJ):​c.2693-592C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,022 control chromosomes in the GnomAD database, including 9,141 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 0.33 (9141 hom., cov: 33)
• Consequence: CENPJ NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5	c.2693-592C>G		intron_variant		ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.2693-592C>G		intron_variant		1	NM_018451.5	ENSP00000371308	P1
CENPJ	ENST00000616936.4	c.2693-592C>G		intron_variant, NMD_transcript_variant		1		ENSP00000477511
CENPJ	ENST00000545981.6	c.2693-592C>G		intron_variant, NMD_transcript_variant		2		ENSP00000441090

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50858 AN: 151904 Hom.: 9133 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.335 AC: 50896 AN: 152022 Hom.: 9141 Cov.: 33 AF XY: 0.340 AC XY: 25261 AN XY: 74284

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.330

Alfa AF: 0.347 Hom.: 1214

Bravo AF: 0.327

Asia WGS AF: 0.360 AC: 1243 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.73

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: rs12871627; hg19: chr13-25478788;