chr11-46766023-T-C

Position:

• chr11-46766023-T-C

Variant summary

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

The NM_001008938.4(CKAP5):​c.3412-767A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,096 control chromosomes in the GnomAD database, including 33,162 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 0.64 (33162 hom., cov: 33)
• Consequence: CKAP5 NM_001008938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990

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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP5	NM_001008938.4	c.3412-767A>G		intron_variant		ENST00000529230.6	NP_001008938.1
CKAP5	NM_014756.4	c.3412-767A>G		intron_variant			NP_055571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP5	ENST00000529230.6	c.3412-767A>G		intron_variant		5	NM_001008938.4	ENSP00000432768	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97723 AN: 151978 Hom.: 33149 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.686

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.643 AC: 97753 AN: 152096 Hom.: 33162 Cov.: 33 AF XY: 0.638 AC XY: 47438 AN XY: 74336

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.691

Alfa AF: 0.754 Hom.: 43216

Bravo AF: 0.630

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.0
DANN	Benign	0.67

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: rs10734548; hg19: chr11-46787573;