1-91502825-T-C

Position:

• chr1-91502825-T-C

Variant summary

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

The NM_003503.4(CDC7):​c.115+994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,176 control chromosomes in the GnomAD database, including 67,401 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 0.94 (67401 hom., cov: 31)
• Consequence: CDC7 NM_003503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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]

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 (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC7	NM_003503.4	c.115+994T>C		intron_variant		ENST00000234626.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC7	ENST00000234626.11	c.115+994T>C		intron_variant		1	NM_003503.4	P1
CDC7	ENST00000428239.5	c.115+994T>C		intron_variant		1		P1
CDC7	ENST00000426137.1	c.115+994T>C		intron_variant		5
CDC7	ENST00000497611.1	n.501+994T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142846 AN: 152058 Hom.: 67371 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.942

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

GnomAD4 genome AF: 0.939 AC: 142934 AN: 152176 Hom.: 67401 Cov.: 31 AF XY: 0.934 AC XY: 69451 AN XY: 74398

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.942

Alfa AF: 0.960 Hom.: 16615

Bravo AF: 0.932

Asia WGS AF: 0.878 AC: 3052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.76

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: rs494244; hg19: chr1-91968382;