rs12871627

Variant names:

• chr13-24904650-G-C
• rs12871627
• NM_018451.5:c.2693-592C>G

Variant summary

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

The NM_018451.5(CPAP):​c.2693-592C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,022 control chromosomes in the GnomAD database, including 9,141 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 0.33 (9141 hom., cov: 33)
• Consequence: CPAP NM_018451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	NM_018451.5	MANE Select	c.2693-592C>G		intron	N/A	NP_060921.3
	CPAP	NR_047594.2		n.2860-592C>G		intron	N/A
	CPAP	NR_047595.2		n.2860-592C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.2693-592C>G		intron	N/A	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000616936.4	TSL:1	n.2693-592C>G		intron	N/A	ENSP00000477511.1	Q9HC77-2
	CPAP	ENST00000926443.1		c.2693-592C>G		intron	N/A	ENSP00000596502.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50858 AN: 151904 Hom.: 9133 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.335 AC: 50896 AN: 152022 Hom.: 9141 Cov.: 33 AF XY: 0.340 AC XY: 25261 AN XY: 74284

African (AFR) AF: 0.195 AC: 8101 AN: 41498

American (AMR) AF: 0.416 AC: 6364 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1588 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2070 AN: 5172

South Asian (SAS) AF: 0.386 AC: 1865 AN: 4826

European-Finnish (FIN) AF: 0.418 AC: 4395 AN: 10510

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25515 AN: 67952

Other (OTH) AF: 0.330 AC: 694 AN: 2106

Alfa AF: 0.347 Hom.: 1214

Bravo AF: 0.327

Asia WGS AF: 0.360 AC: 1243 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.40
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: rs12871627; hg19: chr13-25478788;