rs7108147

Positions:

• chr11-46809297-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008938.4(CKAP5):​c.864+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 707,254 control chromosomes in the GnomAD database, including 5,307 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2550 hom., cov: 32)
  • Exomes 𝑓: 0.085 (2757 hom.)
• Consequence: CKAP5 NM_001008938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

Genes affected

CKAP5 (HGNC:28959): (cytoskeleton associated protein 5) This gene encodes a cytoskeleton-associated protein which belongs to the TOG/XMAP215 family. The N-terminal half of this protein contains a microtubule-binding domain and the C-terminal half contains a KXGS motif for binding tubulin dimers. This protein has two distinct roles in spindle formation; it protects kinetochore microtubules from depolymerization and plays an essential role in centrosomal microtubule assembly. This protein may be necessary for the proper interaction of microtubules with the cell cortex for directional cell movement. It also plays a role in translation of the myelin basic protein (MBP) mRNA by interacting with heterogeneous nuclear ribonucleoprotein (hnRNP) A2, which associates with MBP. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP5	NM_001008938.4	c.864+103C>T		intron_variant		ENST00000529230.6	NP_001008938.1
CKAP5	NM_014756.4	c.864+103C>T		intron_variant			NP_055571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP5	ENST00000529230.6	c.864+103C>T		intron_variant		5	NM_001008938.4	ENSP00000432768	P1
CKAP5	ENST00000354558.7	c.864+103C>T		intron_variant		1		ENSP00000346566
CKAP5	ENST00000312055.9	c.864+103C>T		intron_variant		5		ENSP00000310227

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22540 AN: 152034 Hom.: 2546 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.0849 AC: 47146 AN: 555102 Hom.: 2757 AF XY: 0.0833 AC XY: 24512 AN XY: 294294

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.0552

Gnomad4 ASJ exome AF: 0.0938

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0646

Gnomad4 FIN exome AF: 0.0760

Gnomad4 NFE exome AF: 0.0878

Gnomad4 OTH exome AF: 0.0939

GnomAD4 genome AF: 0.148 AC: 22564 AN: 152152 Hom.: 2550 Cov.: 32 AF XY: 0.146 AC XY: 10836 AN XY: 74408

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.0728

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.132

Alfa AF: 0.102 Hom.: 527

Bravo AF: 0.155

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs7108147; hg19: chr11-46830847;