rs10518820

Variant names:

• chr15-43596778-G-T
• rs10518820
• NM_001375484.1:c.876+247G>T

Variant summary

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

The NM_001375484.1(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 NM_001375484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CKMT1B	NM_001375484.1	c.876+247G>T		intron_variant	Intron 6 of 8	ENST00000441322.6	NP_001362413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKMT1B	ENST00000441322.6	c.876+247G>T		intron_variant	Intron 6 of 8	1	NM_001375484.1	ENSP00000413255.2
CKMT1B	ENST00000300283.10	c.876+247G>T		intron_variant	Intron 7 of 9	5		ENSP00000300283.6
CKMT1B	ENST00000627381.1	c.876+247G>T		intron_variant	Intron 6 of 6	5		ENSP00000486477.1
CKMT1B	ENST00000437534.3	n.876+247G>T		intron_variant	Intron 6 of 8	2		ENSP00000416717.1

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

African (AFR) AF: 0.295 AC: 11607 AN: 39406

American (AMR) AF: 0.176 AC: 2680 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1574 AN: 4892

South Asian (SAS) AF: 0.145 AC: 695 AN: 4786

European-Finnish (FIN) AF: 0.0421 AC: 441 AN: 10478

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.0930 AC: 6315 AN: 67902

Other (OTH) AF: 0.160 AC: 335 AN: 2094

Alfa AF: 0.146 Hom.: 2051

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
PhyloP100		-0.022
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: rs10518820; hg19: chr15-43888976;