dbSNP rs12125947: CDC7:c.*495T>C (chr1-91524930-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

25 publications found

Variant links:

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]

CDC7 links:

ENSG00000308368 (HGNC:):

ENSG00000308368 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDC7	NM_003503.4 link	c.*495T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000234626.11	NP_003494.1	O00311-1A0A384MTU6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDC7	ENST00000234626.11 link	c.*495T>C	3_prime_UTR_variant	Exon 12 of 12	1	NM_003503.4	ENSP00000234626.6	O00311-1
CDC7	ENST00000428239.5 link	c.*495T>C	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000393139.1	O00311-1
ENSG00000308368	ENST00000833639.1 link	n.1291-6255A>G	intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58643

AN:

151816

Hom.:

12460

Cov.:

show subpopulations

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:

AN:

178

Hom.:

Cov.:

AF XY:

0.370

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.600

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.349

AC:

AN:

146

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58661

AN:

151934

Hom.:

12456

Cov.:

AF XY:

0.384

AC XY:

28548

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.269

AC:

11131

AN:

41432

American (AMR)

AF:

0.326

AC:

4979

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1603

AN:

3466

East Asian (EAS)

AF:

0.0778

AC:

403

AN:

5180

South Asian (SAS)

AF:

0.277

AC:

1339

AN:

4828

European-Finnish (FIN)

AF:

0.502

AC:

5295

AN:

10540

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.481

AC:

32650

AN:

67896

Other (OTH)

AF:

0.386

AC:

816

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1724

3448

5173

6897

8621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.440

Hom.:

47553

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

(source)

DANN

Benign

0.86

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over