Variant 1-91513109-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003503.4(CDC7):c.624A>G(p.Ile208Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,452 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

CDC7
NM_003503.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.35

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:

CDC7 (HGNC:):

CDC7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007945299).

BP6

Variant 1-91513109-A-G is Benign according to our data. Variant chr1-91513109-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2672339.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC7	NM_003503.4 linkuse as main transcript	c.624A>G	p.Ile208Met	missense_variant	7/12	ENST00000234626.11	NP_003494.1	O00311-1A0A384MTU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC7	ENST00000234626.11 linkuse as main transcript	c.624A>G	p.Ile208Met	missense_variant	7/12	1	NM_003503.4	ENSP00000234626.6	O00311-1
CDC7	ENST00000428239.5 linkuse as main transcript	c.624A>G	p.Ile208Met	missense_variant	7/12	1		ENSP00000393139.1	O00311-1
CDC7	ENST00000486509.1 linkuse as main transcript	n.-18A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00281

AC:

706

AN:

250946

Hom.:

AF XY:

0.00276

AC XY:

374

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00439

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00317

AC:

4630

AN:

1461192

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

2284

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000919

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.00421

Gnomad4 NFE exome

AF:

0.00362

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152260

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00249

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00331

AC:

402

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00355

EpiControl

AF:

0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

CDC7: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.95

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.43

MVP

0.72

MPC

0.69

ClinPred

0.031

GERP RS

4.4

Varity_R

0.68

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over