chr11-46766023-T-C

Variant names:

• chr11-46766023-T-C
• rs10734548
• NM_001008938.4:c.3412-767A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008938.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP5	NM_001008938.4	MANE Select	c.3412-767A>G		intron	N/A	NP_001008938.1
	CKAP5	NM_014756.4		c.3412-767A>G		intron	N/A	NP_055571.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP5	ENST00000529230.6	TSL:5 MANE Select	c.3412-767A>G		intron	N/A	ENSP00000432768.1
	CKAP5	ENST00000354558.7	TSL:1	c.3412-767A>G		intron	N/A	ENSP00000346566.3
	CKAP5	ENST00000533413.5	TSL:1	n.391-767A>G		intron	N/A

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

African (AFR) AF: 0.431 AC: 17850 AN: 41462

American (AMR) AF: 0.654 AC: 9988 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2813 AN: 3472

East Asian (EAS) AF: 0.394 AC: 2037 AN: 5176

South Asian (SAS) AF: 0.728 AC: 3510 AN: 4822

European-Finnish (FIN) AF: 0.674 AC: 7119 AN: 10562

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52084 AN: 68008

Other (OTH) AF: 0.691 AC: 1459 AN: 2110

Alfa AF: 0.749 Hom.: 50554

Bravo AF: 0.630

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-0.99
Mutation Taster		=100/0	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: rs10734548; hg19: chr11-46787573;