rs9318917

Variant names:

• chr13-24892636-T-C
• rs9318917
• NM_018451.5:c.3216+7A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-24892636-T-C
• chr13-24892636-T-A
• chr13-24892636-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018451.5(CPAP):​c.3216+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,611,198 control chromosomes in the GnomAD database, including 538,374 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46483 hom., cov: 29)
  • Exomes 𝑓: 0.82 (491891 hom.)
• Consequence: CPAP NM_018451.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002216
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.975
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-24892636-T-C is Benign according to our data. Variant chr13-24892636-T-C is described in ClinVar as Benign. ClinVar VariationId is 158208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 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.3216+7A>G		splice_region intron	N/A	NP_060921.3
	CPAP	NR_047594.2		n.3383+7A>G		splice_region intron	N/A
	CPAP	NR_047595.2		n.3383+7A>G		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.3216+7A>G		splice_region intron	N/A	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000418179.1	TSL:1	c.459+7A>G		splice_region intron	N/A	ENSP00000399334.1	H0Y5L8
	CPAP	ENST00000616936.4	TSL:1	n.3216+7A>G		splice_region intron	N/A	ENSP00000477511.1	Q9HC77-2

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118044 AN: 151832 Hom.: 46453 Cov.: 29

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.808 AC: 203202 AN: 251418 AF XY: 0.801

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.880

Gnomad ASJ exome AF: 0.762

Gnomad EAS exome AF: 0.845

Gnomad FIN exome AF: 0.893

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.819 AC: 1195413 AN: 1459248 Hom.: 491891 Cov.: 36 AF XY: 0.815 AC XY: 591576 AN XY: 726116

African (AFR) AF: 0.646 AC: 21589 AN: 33398

American (AMR) AF: 0.873 AC: 39019 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 19883 AN: 26122

East Asian (EAS) AF: 0.864 AC: 34307 AN: 39690

South Asian (SAS) AF: 0.677 AC: 58355 AN: 86186

European-Finnish (FIN) AF: 0.893 AC: 47622 AN: 53350

Middle Eastern (MID) AF: 0.751 AC: 4191 AN: 5580

European-Non Finnish (NFE) AF: 0.831 AC: 922341 AN: 1109912

Other (OTH) AF: 0.798 AC: 48106 AN: 60290

GnomAD4 genome AF: 0.777 AC: 118120 AN: 151950 Hom.: 46483 Cov.: 29 AF XY: 0.778 AC XY: 57782 AN XY: 74268

African (AFR) AF: 0.655 AC: 27092 AN: 41372

American (AMR) AF: 0.820 AC: 12522 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2676 AN: 3468

East Asian (EAS) AF: 0.852 AC: 4414 AN: 5180

South Asian (SAS) AF: 0.665 AC: 3188 AN: 4794

European-Finnish (FIN) AF: 0.888 AC: 9378 AN: 10564

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56311 AN: 67984

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.805 Hom.: 34950

Bravo AF: 0.770

Asia WGS AF: 0.725 AC: 2520 AN: 3478

EpiCase AF: 0.813

EpiControl AF: 0.815

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	4	not provided (4)
-	-	2	Microcephaly 6, primary, autosomal recessive (2)
-	-	2	Seckel syndrome 4 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.088
DANN	Benign	0.32
PhyloP100		-0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.040		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: rs9318917; hg19: chr13-25466774;