rs10220033

Positions:

• chr13-24907740-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018451.5(CENPJ):​c.974+278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,042 control chromosomes in the GnomAD database, including 2,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (2855 hom., cov: 32)
• Consequence: CENPJ NM_018451.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-24907740-C-T is Benign according to our data. Variant chr13-24907740-C-T is described in ClinVar as [Benign]. Clinvar id is 668867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.974+278G>A		intron_variant		ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.974+278G>A		intron_variant		1	NM_018451.5	P1
CENPJ	ENST00000616936.4	c.974+278G>A		intron_variant, NMD_transcript_variant		1
CENPJ	ENST00000545981.6	c.974+278G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28207 AN: 151924 Hom.: 2847 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.186 AC: 28223 AN: 152042 Hom.: 2855 Cov.: 32 AF XY: 0.185 AC XY: 13780 AN XY: 74314

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0920

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.220

Alfa AF: 0.166 Hom.: 285

Bravo AF: 0.187

Asia WGS AF: 0.243 AC: 844 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.60

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: rs10220033; hg19: chr13-25481878;