13-24895016-C-T

Variant names:

• chr13-24895016-C-T
• rs11616836
• NM_018451.5:c.2992-2149G>A

Variant summary

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

The NM_018451.5(CPAP):​c.2992-2149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,294 control chromosomes in the GnomAD database, including 198 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 0.040 (198 hom., cov: 33)
• Consequence: CPAP NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAP	NM_018451.5	c.2992-2149G>A		intron_variant	Intron 9 of 16	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.2992-2149G>A		intron_variant	Intron 9 of 16	1	NM_018451.5	ENSP00000371308.4
CENPJ	ENST00000418179.1	c.235-2149G>A		intron_variant	Intron 2 of 3	1		ENSP00000399334.1
CENPJ	ENST00000616936.4	n.2992-2149G>A		intron_variant	Intron 9 of 15	1		ENSP00000477511.1
CENPJ	ENST00000545981.6	n.2992-2149G>A		intron_variant	Intron 9 of 17	2		ENSP00000441090.2

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6109 AN: 152176 Hom.: 195 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0402 AC: 6116 AN: 152294 Hom.: 198 Cov.: 33 AF XY: 0.0391 AC XY: 2910 AN XY: 74468

African (AFR) AF: 0.0106 AC: 441 AN: 41568

American (AMR) AF: 0.0806 AC: 1234 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 97 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.0440 AC: 212 AN: 4822

European-Finnish (FIN) AF: 0.0397 AC: 422 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3602 AN: 68020

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0484 Hom.: 366

Bravo AF: 0.0430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.53
DANN	Benign	0.90
PhyloP100		-2.7
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: rs11616836; hg19: chr13-25469154;