chr1-47333967-G-C

Variant names:

• chr1-47333967-G-C
• rs7543016
• NM_016308.3:c.22G>C

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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
• Publications: 39 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016308.3. 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
	CMPK1	NM_016308.3	MANE Select	c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	NP_057392.1
	CMPK1	NM_001136140.2		c.22G>C	p.Gly8Arg	missense	Exon 1 of 5	NP_001129612.1
	CMPK1	NM_001366135.1		c.-75G>C		5_prime_UTR	Exon 1 of 6	NP_001353064.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMPK1	ENST00000371873.10	TSL:1 MANE Select	c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	ENSP00000360939.5
	CMPK1	ENST00000954782.1		c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	ENSP00000624841.1
	CMPK1	ENST00000954781.1		c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	ENSP00000624840.1

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

GnomAD2 exomes AF: 0.472 AC: 70933 AN: 150196 AF XY: 0.465

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 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

African (AFR) AF: 0.801 AC: 22226 AN: 27754

American (AMR) AF: 0.552 AC: 19089 AN: 34594

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 8324 AN: 22888

East Asian (EAS) AF: 0.616 AC: 18906 AN: 30716

South Asian (SAS) AF: 0.466 AC: 34391 AN: 73724

European-Finnish (FIN) AF: 0.360 AC: 17064 AN: 47344

Middle Eastern (MID) AF: 0.476 AC: 1792 AN: 3762

European-Non Finnish (NFE) AF: 0.496 AC: 518696 AN: 1046006

Other (OTH) AF: 0.501 AC: 27057 AN: 53962

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

African (AFR) AF: 0.789 AC: 32662 AN: 41384

American (AMR) AF: 0.565 AC: 8582 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1202 AN: 3454

East Asian (EAS) AF: 0.583 AC: 2970 AN: 5096

South Asian (SAS) AF: 0.453 AC: 2182 AN: 4812

European-Finnish (FIN) AF: 0.356 AC: 3616 AN: 10158

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.486 AC: 32814 AN: 67564

Other (OTH) AF: 0.532 AC: 1115 AN: 2094

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
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
MetaRNN	Benign	8.0e-7	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.049
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.056
Sift	Benign	1.0	T
Sift4G	Benign	0.72	T
Vest4		0.23
MutPred		0.36		Gain of MoRF binding (P = 0.0023)
MPC		1.2
ClinPred		0.0027	T
GERP RS		2.9
PromoterAI		-0.0087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.30
Mutation Taster		=97/3	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: rs7543016; hg19: chr1-47799639; COSMIC: COSV64101982;