rs10518820

Positions:

• chr15-43596778-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441322.6(CKMT1B):​c.876+247G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 149,438 control chromosomes in the GnomAD database, including 4,049 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 0.16 (4049 hom., cov: 28)
• Consequence: CKMT1B ENST00000441322.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

Genes affected

CKMT1B (HGNC:1995): (creatine kinase, mitochondrial 1B) Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 have been identified which encode identical mitochondrial creatine kinase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKMT1B	NM_001375484.1	c.876+247G>T		intron_variant		ENST00000441322.6	NP_001362413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKMT1B	ENST00000441322.6	c.876+247G>T		intron_variant		1	NM_001375484.1	ENSP00000413255	P1
CKMT1B	ENST00000300283.10	c.876+247G>T		intron_variant		5		ENSP00000300283	P1
CKMT1B	ENST00000627381.1	c.876+247G>T		intron_variant		5		ENSP00000486477
CKMT1B	ENST00000437534.3	c.876+247G>T		intron_variant, NMD_transcript_variant		2		ENSP00000416717

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24383 AN: 149324 Hom.: 4036 Cov.: 28

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.163 AC: 24432 AN: 149438 Hom.: 4049 Cov.: 28 AF XY: 0.161 AC XY: 11749 AN XY: 73012

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0930

Gnomad4 OTH AF: 0.160

Alfa AF: 0.118 Hom.: 872

Bravo AF: 0.185

Asia WGS AF: 0.229 AC: 782 AN: 3412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.55

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: rs10518820; hg19: chr15-43888976;