chr13-24882866-ACTT-A

Variant names:

• chr13-24882866-ACTT-A
• rs796638364
• NM_018451.5:c.*308_*310delAAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018451.5(CPAP):​c.*308_*310delAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 356,646 control chromosomes in the GnomAD database, including 11,291 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4108 hom., cov: 23)
  • Exomes 𝑓: 0.25 (7183 hom.)
• Consequence: CPAP NM_018451.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.254
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 13-24882866-ACTT-A is Benign according to our data. Variant chr13-24882866-ACTT-A is described in ClinVar as Benign. ClinVar VariationId is 311599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 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.*308_*310delAAG		3_prime_UTR	Exon 17 of 17	NP_060921.3
	CPAP	NR_047594.2		n.4609_4611delAAG		non_coding_transcript_exon	Exon 18 of 18
	CPAP	NR_047595.2		n.4407_4409delAAG		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.*308_*310delAAG		3_prime_UTR	Exon 17 of 17	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000616936.4	TSL:1	n.*979_*981delAAG		non_coding_transcript_exon	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2
	CPAP	ENST00000616936.4	TSL:1	n.*979_*981delAAG		3_prime_UTR	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 33369 AN: 145168 Hom.: 4111 Cov.: 23

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.248 AC: 52454 AN: 211384 Hom.: 7183 AF XY: 0.242 AC XY: 27856 AN XY: 114896

African (AFR) AF: 0.121 AC: 705 AN: 5842

American (AMR) AF: 0.197 AC: 1744 AN: 8870

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 1451 AN: 5636

East Asian (EAS) AF: 0.0479 AC: 468 AN: 9776

South Asian (SAS) AF: 0.175 AC: 6093 AN: 34874

European-Finnish (FIN) AF: 0.267 AC: 2586 AN: 9678

Middle Eastern (MID) AF: 0.208 AC: 179 AN: 862

European-Non Finnish (NFE) AF: 0.292 AC: 36436 AN: 124750

Other (OTH) AF: 0.252 AC: 2792 AN: 11096

GnomAD4 genome AF: 0.230 AC: 33351 AN: 145262 Hom.: 4108 Cov.: 23 AF XY: 0.226 AC XY: 15999 AN XY: 70942

African (AFR) AF: 0.130 AC: 4986 AN: 38448

American (AMR) AF: 0.206 AC: 3021 AN: 14698

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 908 AN: 3286

East Asian (EAS) AF: 0.0536 AC: 274 AN: 5116

South Asian (SAS) AF: 0.189 AC: 804 AN: 4260

European-Finnish (FIN) AF: 0.255 AC: 2636 AN: 10342

Middle Eastern (MID) AF: 0.214 AC: 57 AN: 266

European-Non Finnish (NFE) AF: 0.300 AC: 19772 AN: 66006

Other (OTH) AF: 0.234 AC: 463 AN: 1976

Alfa AF: 0.164 Hom.: 385

Bravo AF: 0.212

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary Microcephaly, Recessive (1)
-	-	1	Seckel syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs796638364; hg19: chr13-25457004; COSMIC: COSV55038561; COSMIC: COSV55038561;