rs7108147

Variant names:

• chr11-46809297-G-A
• rs7108147
• NM_001008938.4:c.864+103C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.317 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.864+103C>T		intron	N/A	NP_001008938.1	Q14008-1
	CKAP5	NM_014756.4		c.864+103C>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.864+103C>T		intron	N/A	ENSP00000432768.1	Q14008-1
	CKAP5	ENST00000354558.7	TSL:1	c.864+103C>T		intron	N/A	ENSP00000346566.3	Q14008-2
	CKAP5	ENST00000928128.1		c.864+103C>T		intron	N/A	ENSP00000598187.1

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

African (AFR) AF: 0.321 AC: 4454 AN: 13862

American (AMR) AF: 0.0552 AC: 1189 AN: 21524

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 1425 AN: 15196

East Asian (EAS) AF: 0.000126 AC: 4 AN: 31758

South Asian (SAS) AF: 0.0646 AC: 3137 AN: 48588

European-Finnish (FIN) AF: 0.0760 AC: 3518 AN: 46294

Middle Eastern (MID) AF: 0.123 AC: 274 AN: 2224

European-Non Finnish (NFE) AF: 0.0878 AC: 30381 AN: 346212

Other (OTH) AF: 0.0939 AC: 2764 AN: 29444

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

African (AFR) AF: 0.322 AC: 13346 AN: 41468

American (AMR) AF: 0.0758 AC: 1159 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0657 AC: 317 AN: 4826

European-Finnish (FIN) AF: 0.0728 AC: 771 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6159 AN: 68004

Other (OTH) AF: 0.132 AC: 279 AN: 2110

Alfa AF: 0.102 Hom.: 616

Bravo AF: 0.155

Asia WGS AF: 0.0420 AC: 147 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	0.29
DANN	Benign	0.38
PhyloP100		-0.38
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: rs7108147; hg19: chr11-46830847;