rs1007738

Positions:

• chr11-46827809-G-A
• chr11-46827809-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

CKAP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP5	NM_001008938.4	c.-37-6541C>T		intron_variant		ENST00000529230.6	NP_001008938.1
CKAP5	NM_014756.4	c.-37-6541C>T		intron_variant			NP_055571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP5	ENST00000529230.6	c.-37-6541C>T		intron_variant		5	NM_001008938.4	ENSP00000432768.1
CKAP5	ENST00000312055.9	c.-37-6541C>T		intron_variant		5		ENSP00000310227.5
CKAP5	ENST00000525248.1	n.78-6561C>T		intron_variant		3

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

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.693

Alfa AF: 0.750 Hom.: 101174

Bravo AF: 0.633

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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