rs1029113

Variant names:

• chr13-24916255-C-G
• rs1029113
• NM_018451.5:c.-66-3164G>C

Variant summary

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

The NM_018451.5(CPAP):​c.-66-3164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,002 control chromosomes in the GnomAD database, including 27,814 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 0.59 (27814 hom., cov: 31)
• Consequence: CPAP NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAP	NM_018451.5	c.-66-3164G>C		intron_variant	Intron 1 of 16	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.-66-3164G>C		intron_variant	Intron 1 of 16	1	NM_018451.5	ENSP00000371308.4
CENPJ	ENST00000616936.4	n.-66-3164G>C		intron_variant	Intron 1 of 15	1		ENSP00000477511.1
CENPJ	ENST00000545981.6	n.-66-3164G>C		intron_variant	Intron 1 of 17	2		ENSP00000441090.2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89761 AN: 151884 Hom.: 27793 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.591 AC: 89815 AN: 152002 Hom.: 27814 Cov.: 31 AF XY: 0.595 AC XY: 44196 AN XY: 74306

African (AFR) AF: 0.401 AC: 16610 AN: 41424

American (AMR) AF: 0.666 AC: 10165 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2183 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3744 AN: 5178

South Asian (SAS) AF: 0.555 AC: 2671 AN: 4810

European-Finnish (FIN) AF: 0.739 AC: 7800 AN: 10552

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.660 AC: 44869 AN: 67986

Other (OTH) AF: 0.576 AC: 1217 AN: 2114

Alfa AF: 0.619 Hom.: 3741

Bravo AF: 0.580

Asia WGS AF: 0.601 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.28
DANN	Benign	0.57
PhyloP100		-1.2
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: rs1029113; hg19: chr13-25490393;