rs17081368

Variant names:

• chr13-24906478-T-A
• rs17081368
• NM_018451.5:c.1560A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-24906478-T-A
• chr13-24906478-T-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018451.5(CPAP):​c.1560A>T​(p.Thr520Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 1,614,184 control chromosomes in the GnomAD database, including 941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (478 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (463 hom.)
• Consequence: CPAP NM_018451.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0200
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-24906478-T-A is Benign according to our data. Variant chr13-24906478-T-A is described in ClinVar as Benign. ClinVar VariationId is 136718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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.1560A>T	p.Thr520Thr	synonymous	Exon 7 of 17	NP_060921.3
	CPAP	NR_047594.2		n.1727A>T		non_coding_transcript_exon	Exon 7 of 18
	CPAP	NR_047595.2		n.1727A>T		non_coding_transcript_exon	Exon 7 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.1560A>T	p.Thr520Thr	synonymous	Exon 7 of 17	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000616936.4	TSL:1	n.1560A>T		non_coding_transcript_exon	Exon 7 of 16	ENSP00000477511.1	Q9HC77-2
	CPAP	ENST00000926443.1		c.1560A>T	p.Thr520Thr	synonymous	Exon 7 of 18	ENSP00000596502.1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6753 AN: 152184 Hom.: 474 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0118 AC: 2959 AN: 251130 AF XY: 0.00825

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00720

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000828

Gnomad OTH exome AF: 0.00865

GnomAD4 exome AF: 0.00490 AC: 7164 AN: 1461882 Hom.: 463 Cov.: 34 AF XY: 0.00412 AC XY: 2993 AN XY: 727246

African (AFR) AF: 0.162 AC: 5412 AN: 33480

American (AMR) AF: 0.00798 AC: 357 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.0180 AC: 104 AN: 5768

European-Non Finnish (NFE) AF: 0.000504 AC: 561 AN: 1112010

Other (OTH) AF: 0.0115 AC: 693 AN: 60396

GnomAD4 genome AF: 0.0445 AC: 6778 AN: 152302 Hom.: 478 Cov.: 33 AF XY: 0.0421 AC XY: 3133 AN XY: 74486

African (AFR) AF: 0.153 AC: 6375 AN: 41552

American (AMR) AF: 0.0171 AC: 262 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68018

Other (OTH) AF: 0.0326 AC: 69 AN: 2116

Alfa AF: 0.0137 Hom.: 39

Bravo AF: 0.0495

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (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	-0.88
CADD	Benign	0.20
DANN	Benign	0.40
PhyloP100		0.020
Mutation Taster		=98/2	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: rs17081368; hg19: chr13-25480616;