rs34991318

Variant names:

• chr13-24884094-AGTT-A
• rs34991318
• NM_018451.5:c.3704-14_3704-12delAAC

Your query was ambiguous. Multiple possible variants found:

• chr13-24884094-AGTT-A
• chr13-24884094-AGTT-AGTTGTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018451.5(CPAP):​c.3704-14_3704-12delAAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,611,820 control chromosomes in the GnomAD database, including 243,098 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19947 hom., cov: 0)
  • Exomes 𝑓: 0.55 (223151 hom.)
• Consequence: CPAP NM_018451.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 2.18
• Publications: 8 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 -16 ACMG points.

• BP6: Variant 13-24884094-AGTT-A is Benign according to our data. Variant chr13-24884094-AGTT-A is described in ClinVar as Benign. ClinVar VariationId is 158213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 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.3704-14_3704-12delAAC		intron	N/A	NP_060921.3
	CPAP	NR_047594.2		n.3988-14_3988-12delAAC		intron	N/A
	CPAP	NR_047595.2		n.3786-14_3786-12delAAC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.3704-14_3704-12delAAC		intron	N/A	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000616936.4	TSL:1	n.*358-14_*358-12delAAC		intron	N/A	ENSP00000477511.1	Q9HC77-2
	CPAP	ENST00000926443.1		c.3785-14_3785-12delAAC		intron	N/A	ENSP00000596502.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75604 AN: 151688 Hom.: 19923 Cov.: 0

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.504

GnomAD2 exomes AF: 0.562 AC: 139681 AN: 248620 AF XY: 0.555

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.505

Gnomad EAS exome AF: 0.799

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.548 AC: 800492 AN: 1460016 Hom.: 223151 AF XY: 0.546 AC XY: 396853 AN XY: 726442

African (AFR) AF: 0.324 AC: 10852 AN: 33446

American (AMR) AF: 0.668 AC: 29842 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 13093 AN: 26124

East Asian (EAS) AF: 0.816 AC: 32378 AN: 39694

South Asian (SAS) AF: 0.499 AC: 43026 AN: 86236

European-Finnish (FIN) AF: 0.624 AC: 33297 AN: 53400

Middle Eastern (MID) AF: 0.484 AC: 2789 AN: 5758

European-Non Finnish (NFE) AF: 0.543 AC: 602786 AN: 1110324

Other (OTH) AF: 0.537 AC: 32429 AN: 60336

GnomAD4 genome AF: 0.498 AC: 75657 AN: 151804 Hom.: 19947 Cov.: 0 AF XY: 0.505 AC XY: 37497 AN XY: 74178

African (AFR) AF: 0.335 AC: 13884 AN: 41448

American (AMR) AF: 0.601 AC: 9179 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3468

East Asian (EAS) AF: 0.798 AC: 4109 AN: 5150

South Asian (SAS) AF: 0.495 AC: 2387 AN: 4820

European-Finnish (FIN) AF: 0.632 AC: 6631 AN: 10484

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 36227 AN: 67840

Other (OTH) AF: 0.500 AC: 1056 AN: 2110

Alfa AF: 0.443 Hom.: 2287

Bravo AF: 0.493

Asia WGS AF: 0.598 AC: 2074 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=88/12	polymorphism

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: rs34991318; hg19: chr13-25458232;