rs12125947

Positions:

• chr1-91524930-T-C
• chr1-91524930-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003503.4(CDC7):​c.*495T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,112 control chromosomes in the GnomAD database, including 12,470 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 0.39 (12456 hom., cov: 32)
  • Exomes 𝑓: 0.35 (14 hom.)
• Consequence: CDC7 NM_003503.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

CDC7 (HGNC:1745): (cell division cycle 7) This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected. [provided by RefSeq, Aug 2008]

LOC102723436 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC7	NM_003503.4	c.*495T>C		3_prime_UTR_variant	12/12	ENST00000234626.11	NP_003494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC7	ENST00000234626.11	c.*495T>C		3_prime_UTR_variant	12/12	1	NM_003503.4	ENSP00000234626.6
CDC7	ENST00000428239.5	c.*495T>C		3_prime_UTR_variant	12/12	1		ENSP00000393139.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58643 AN: 151816 Hom.: 12460 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.348 AC: 62 AN: 178 Hom.: 14 Cov.: 0 AF XY: 0.370 AC XY: 34 AN XY: 92

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.386 AC: 58661 AN: 151934 Hom.: 12456 Cov.: 32 AF XY: 0.384 AC XY: 28548 AN XY: 74284

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.386

Alfa AF: 0.449 Hom.: 20739

Bravo AF: 0.369

Asia WGS AF: 0.165 AC: 575 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.86

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: rs12125947; hg19: chr1-91990487; COSMIC: COSV52309973; COSMIC: COSV52309973;