chr1-47333967-G-C

Position:

• chr1-47333967-G-C

Variant summary

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

The NM_016308.3(CMPK1):​c.22G>C​(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,491,702 control chromosomes in the GnomAD database, including 195,300 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (26009 hom., cov: 31)
  • Exomes 𝑓: 0.50 (169291 hom.)
• Consequence: CMPK1 NM_016308.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

Genes affected

CMPK1 (HGNC:18170): (cytidine/uridine monophosphate kinase 1) This gene encodes one of the enzymes required for cellular nucleic acid biosynthesis. This enzyme catalyzes the transfer of a phosphate group from ATP to CMP, UMP, or dCMP, to form the corresponding diphosphate nucleotide. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Feb 2012]

CMPK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.0106025E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMPK1	NM_016308.3	c.22G>C	p.Gly8Arg	missense_variant	1/6	ENST00000371873.10	NP_057392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMPK1	ENST00000371873.10	c.22G>C	p.Gly8Arg	missense_variant	1/6	1	NM_016308.3	ENSP00000360939.5

Frequencies

GnomAD3 genomes AF: 0.568 AC: 85692 AN: 150844 Hom.: 25980 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.536

GnomAD3 exomes AF: 0.472 AC: 70933 AN: 150196 Hom.: 17339 AF XY: 0.465 AC XY: 38722 AN XY: 83256

Gnomad AFR exome AF: 0.782

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.562

Gnomad SAS exome AF: 0.459

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.498 AC: 667545 AN: 1340750 Hom.: 169291 Cov.: 37 AF XY: 0.495 AC XY: 328840 AN XY: 664930

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.568 AC: 85762 AN: 150952 Hom.: 26009 Cov.: 31 AF XY: 0.562 AC XY: 41442 AN XY: 73708

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.532

Alfa AF: 0.439 Hom.: 4104

Bravo AF: 0.595

TwinsUK AF: 0.497 AC: 1843

ALSPAC AF: 0.499 AC: 1925

ESP6500AA AF: 0.762 AC: 3307

ESP6500EA AF: 0.470 AC: 4001

ExAC AF: 0.443 AC: 50962

Asia WGS AF: 0.503 AC: 1708 AN: 3390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.1
DANN	Benign	0.29
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.16	T;T;T
MetaRNN	Benign	8.0e-7	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Benign	0.056
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.72	T;T;T
Vest4		0.23
MutPred		0.36		Gain of MoRF binding (P = 0.0023);Gain of MoRF binding (P = 0.0023);Gain of MoRF binding (P = 0.0023);
MPC		1.2
ClinPred		0.0027	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.30

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: rs7543016; hg19: chr1-47799639; COSMIC: COSV64101982;