rs1007738

Variant names:

• chr11-46827809-G-A
• rs1007738
• NM_001008938.4:c.-37-6541C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-46827809-G-A
• chr11-46827809-G-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.-37-6541C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,932 control chromosomes in the GnomAD database, including 33,301 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 0.65 (33301 hom., cov: 31)
• Consequence: CKAP5 NM_001008938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794
• Publications: 33 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=-0.86).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP5	NM_001008938.4	MANE Select	c.-37-6541C>T		intron	N/A	NP_001008938.1	Q14008-1
	CKAP5	NM_014756.4		c.-37-6541C>T		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.-37-6541C>T		intron	N/A	ENSP00000432768.1	Q14008-1
	CKAP5	ENST00000928128.1		c.-37-6541C>T		intron	N/A	ENSP00000598187.1
	CKAP5	ENST00000928119.1		c.-37-6541C>T		intron	N/A	ENSP00000598178.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98128 AN: 151812 Hom.: 33286 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.646 AC: 98164 AN: 151932 Hom.: 33301 Cov.: 31 AF XY: 0.641 AC XY: 47613 AN XY: 74268

African (AFR) AF: 0.444 AC: 18368 AN: 41384

American (AMR) AF: 0.655 AC: 9998 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2756 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2031 AN: 5172

South Asian (SAS) AF: 0.726 AC: 3501 AN: 4822

European-Finnish (FIN) AF: 0.674 AC: 7105 AN: 10534

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

European-Non Finnish (NFE) AF: 0.766 AC: 52051 AN: 67976

Other (OTH) AF: 0.693 AC: 1462 AN: 2110

Alfa AF: 0.727 Hom.: 142422

Bravo AF: 0.633

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.67
PhyloP100		0.79
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: rs1007738; hg19: chr11-46849360;