rs9553464

Variant names:

• chr13-24900707-G-A
• rs9553464
• NM_018451.5:c.2826-1123C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018451.5(CPAP):​c.2826-1123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,026 control chromosomes in the GnomAD database, including 17,626 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 0.48 (17626 hom., cov: 32)
• Consequence: CPAP NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 3 publications found

Genes affected

CPAP (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]

CPAP Gene-Disease associations (from GenCC):

• microcephaly 6 with or without short stature

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• microcephaly 6, primary, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAP	NM_018451.5	c.2826-1123C>T		intron_variant	Intron 8 of 16	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.2826-1123C>T		intron_variant	Intron 8 of 16	1	NM_018451.5	ENSP00000371308.4
CENPJ	ENST00000418179.1	c.69-1123C>T		intron_variant	Intron 1 of 3	1		ENSP00000399334.1
CENPJ	ENST00000616936.4	n.2826-1123C>T		intron_variant	Intron 8 of 15	1		ENSP00000477511.1
CENPJ	ENST00000545981.6	n.2826-1123C>T		intron_variant	Intron 8 of 17	2		ENSP00000441090.2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72679 AN: 151908 Hom.: 17596 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.478 AC: 72741 AN: 152026 Hom.: 17626 Cov.: 32 AF XY: 0.475 AC XY: 35281 AN XY: 74318

African (AFR) AF: 0.558 AC: 23146 AN: 41450

American (AMR) AF: 0.431 AC: 6585 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3472

East Asian (EAS) AF: 0.416 AC: 2151 AN: 5172

South Asian (SAS) AF: 0.491 AC: 2364 AN: 4814

European-Finnish (FIN) AF: 0.433 AC: 4576 AN: 10572

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30962 AN: 67954

Other (OTH) AF: 0.491 AC: 1035 AN: 2106

Alfa AF: 0.461 Hom.: 27354

Bravo AF: 0.482

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.85
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9553464; hg19: chr13-25474845;