11-46777081-A-G

Variant names:

• chr11-46777081-A-G
• rs6485690
• NM_001008938.4:c.2862+358T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008938.4(CKAP5):​c.2862+358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,024 control chromosomes in the GnomAD database, including 23,235 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 0.51 (23235 hom., cov: 32)
• Consequence: CKAP5 NM_001008938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP5	NM_001008938.4	MANE Select	c.2862+358T>C		intron	N/A	NP_001008938.1	Q14008-1
	CKAP5	NM_014756.4		c.2862+358T>C		intron	N/A	NP_055571.2	Q14008-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP5	ENST00000529230.6	TSL:5 MANE Select	c.2862+358T>C		intron	N/A	ENSP00000432768.1	Q14008-1
	CKAP5	ENST00000354558.7	TSL:1	c.2862+358T>C		intron	N/A	ENSP00000346566.3	Q14008-2
	CKAP5	ENST00000928128.1		c.2889+358T>C		intron	N/A	ENSP00000598187.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78116 AN: 151906 Hom.: 23224 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.514 AC: 78131 AN: 152024 Hom.: 23235 Cov.: 32 AF XY: 0.514 AC XY: 38176 AN XY: 74312

African (AFR) AF: 0.208 AC: 8612 AN: 41494

American (AMR) AF: 0.566 AC: 8633 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2538 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1530 AN: 5170

South Asian (SAS) AF: 0.669 AC: 3226 AN: 4820

European-Finnish (FIN) AF: 0.618 AC: 6513 AN: 10538

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45096 AN: 67966

Other (OTH) AF: 0.577 AC: 1218 AN: 2110

Alfa AF: 0.647 Hom.: 47662

Bravo AF: 0.494

Asia WGS AF: 0.528 AC: 1832 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.47
PhyloP100		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6485690; hg19: chr11-46798631;