1-91502825-T-C

Variant names:

• chr1-91502825-T-C
• rs494244
• NM_003503.4:c.115+994T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003503.4. 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
	CDC7	NM_003503.4	MANE Select	c.115+994T>C		intron	N/A	NP_003494.1	O00311-1
	CDC7	NM_001134419.2		c.115+994T>C		intron	N/A	NP_001127891.1	A0A384MTU6
	CDC7	NM_001134420.2		c.115+994T>C		intron	N/A	NP_001127892.1	A0A384MTU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC7	ENST00000234626.11	TSL:1 MANE Select	c.115+994T>C		intron	N/A	ENSP00000234626.6	O00311-1
	CDC7	ENST00000428239.5	TSL:1	c.115+994T>C		intron	N/A	ENSP00000393139.1	O00311-1
	CDC7	ENST00000897932.1		c.115+994T>C		intron	N/A	ENSP00000567991.1

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

African (AFR) AF: 0.904 AC: 37534 AN: 41510

American (AMR) AF: 0.840 AC: 12826 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3326 AN: 3470

East Asian (EAS) AF: 0.833 AC: 4300 AN: 5162

South Asian (SAS) AF: 0.929 AC: 4480 AN: 4822

European-Finnish (FIN) AF: 0.923 AC: 9770 AN: 10580

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67509 AN: 68036

Other (OTH) AF: 0.942 AC: 1991 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.76
PhyloP100		-1.1
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: rs494244; hg19: chr1-91968382;