rs3742163

Variant names:

• chr13-24885398-A-G
• rs3742163
• NM_018451.5:c.3367-12T>C

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.3367-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,575,374 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (238 hom.)
• Consequence: CPAP NM_018451.5 intron
• Scores: Splicing: ADA: 0.0001613
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.06
• Publications: 2 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]

RNF17 (HGNC:10060): (ring finger protein 17) This gene is similar to a mouse gene that encodes a testis-specific protein containing a RING finger domain. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-24885398-A-G is Benign according to our data. Variant chr13-24885398-A-G is described in ClinVar as Benign. ClinVar VariationId is 158209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0744 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.3367-12T>C		intron	N/A	NP_060921.3
	CPAP	NR_047594.2		n.3651-12T>C		intron	N/A
	CPAP	NR_047595.2		n.3449-12T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.3367-12T>C		intron	N/A	ENSP00000371308.4
	CPAP	ENST00000616936.4	TSL:1	n.*21-12T>C		intron	N/A	ENSP00000477511.1
	CPAP	ENST00000926443.1		c.3448-12T>C		intron	N/A	ENSP00000596502.1

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 808 AN: 152148 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.000870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.0115 AC: 2884 AN: 251446 AF XY: 0.0100

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.0277

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.0866

Gnomad FIN exome AF: 0.00457

Gnomad NFE exome AF: 0.000826

Gnomad OTH exome AF: 0.00700

GnomAD4 exome AF: 0.00468 AC: 6654 AN: 1423108 Hom.: 238 Cov.: 25 AF XY: 0.00447 AC XY: 3175 AN XY: 710642

African (AFR) AF: 0.000733 AC: 24 AN: 32734

American (AMR) AF: 0.0258 AC: 1151 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.000618 AC: 16 AN: 25882

East Asian (EAS) AF: 0.104 AC: 4102 AN: 39522

South Asian (SAS) AF: 0.00295 AC: 252 AN: 85394

European-Finnish (FIN) AF: 0.00530 AC: 283 AN: 53396

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5694

European-Non Finnish (NFE) AF: 0.000452 AC: 487 AN: 1076798

Other (OTH) AF: 0.00568 AC: 335 AN: 59030

GnomAD4 genome AF: 0.00532 AC: 810 AN: 152266 Hom.: 22 Cov.: 33 AF XY: 0.00607 AC XY: 452 AN XY: 74470

African (AFR) AF: 0.000867 AC: 36 AN: 41516

American (AMR) AF: 0.0155 AC: 237 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0808 AC: 419 AN: 5186

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4822

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68028

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00269 Hom.: 3

Bravo AF: 0.00708

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Microcephaly 6, primary, autosomal recessive (1)
-	-	1	Seckel syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.58
PhyloP100		1.1
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	0.00016
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.17		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: rs3742163; hg19: chr13-25459536; COSMIC: COSV67883514; COSMIC: COSV67883514;