rs12864973

Variant names:

• chr13-24885132-C-T
• rs12864973
• NM_018451.5:c.3477+144G>A

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.3477+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 650,076 control chromosomes in the GnomAD database, including 11,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2059 hom., cov: 33)
  • Exomes 𝑓: 0.18 (9001 hom.)
• Consequence: CENPJ NM_018451.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.841

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]

RNF17 (HGNC:10060): (ring finger protein 17) This gene is similar to a mouse gene that encodes a testis-specific protein containing a RING finger domain. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-24885132-C-T is Benign according to our data. Variant chr13-24885132-C-T is described in ClinVar as [Benign]. Clinvar id is 680183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPJ	NM_018451.5	c.3477+144G>A		intron_variant	Intron 13 of 16	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.3477+144G>A		intron_variant	Intron 13 of 16	1	NM_018451.5	ENSP00000371308.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21782 AN: 152076 Hom.: 2052 Cov.: 33

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.178 AC: 88701 AN: 497882 Hom.: 9001 AF XY: 0.177 AC XY: 47404 AN XY: 267470

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.143 AC: 21802 AN: 152194 Hom.: 2059 Cov.: 33 AF XY: 0.151 AC XY: 11235 AN XY: 74424

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.140

Alfa AF: 0.155 Hom.: 1868

Bravo AF: 0.140

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.89
CADD	Benign	1.3
DANN	Benign	0.54

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: rs12864973; hg19: chr13-25459270;