NM_030928.4:c.1587C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030928.4(CDT1):c.1587C>G(p.Leu529Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,607,606 control chromosomes in the GnomAD database, including 129,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L529L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.48 ( 19477 hom., cov: 35)

Exomes 𝑓: 0.38 ( 110035 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.176

Publications

18 publications found

Variant links:

Genes affected

CDT1 (HGNC:24576): (chromatin licensing and DNA replication factor 1) The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]

CDT1 Gene-Disease associations (from GenCC):

Meier-Gorlin syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
Meier-Gorlin syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-88808224-C-G is Benign according to our data. Variant chr16-88808224-C-G is described in ClinVar as [Benign]. Clinvar id is 128673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.176 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.1587C>G	p.Leu529Leu	synonymous_variant	Exon 10 of 10	ENST00000301019.9	NP_112190.2	Q9H211

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9 link	c.1587C>G	p.Leu529Leu	synonymous_variant	Exon 10 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73391

AN:

152086

Hom.:

19443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.513

GnomAD2 exomes

AF:

0.428

AC:

102108

AN:

238566

AF XY:

0.420

show subpopulations

Gnomad AFR exome

AF:

0.706

Gnomad AMR exome

AF:

0.424

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.692

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.379

AC:

551513

AN:

1455400

Hom.:

110035

Cov.:

AF XY:

0.379

AC XY:

274565

AN XY:

723554

show subpopulations

African (AFR)

AF:

0.719

AC:

24039

AN:

33424

American (AMR)

AF:

0.434

AC:

19023

AN:

43842

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

13465

AN:

25942

East Asian (EAS)

AF:

0.708

AC:

27997

AN:

39546

South Asian (SAS)

AF:

0.393

AC:

33605

AN:

85456

European-Finnish (FIN)

AF:

0.336

AC:

17368

AN:

51718

Middle Eastern (MID)

AF:

0.539

AC:

3104

AN:

5764

European-Non Finnish (NFE)

AF:

0.349

AC:

387549

AN:

1109520

Other (OTH)

AF:

0.421

AC:

25363

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

19993

39986

59980

79973

99966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12620

25240

37860

50480

63100

<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:

0.483

AC:

73471

AN:

152206

Hom.:

19477

Cov.:

AF XY:

0.481

AC XY:

35764

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.700

AC:

29046

AN:

41520

American (AMR)

AF:

0.461

AC:

7045

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1803

AN:

3472

East Asian (EAS)

AF:

0.694

AC:

3587

AN:

5170

South Asian (SAS)

AF:

0.390

AC:

1880

AN:

4820

European-Finnish (FIN)

AF:

0.339

AC:

3591

AN:

10602

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24875

AN:

68008

Other (OTH)

AF:

0.509

AC:

1077

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1907

3815

5722

7630

9537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.361

Hom.:

3147

Bravo

AF:

0.505

Asia WGS

AF:

0.531

AC:

1850

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meier-Gorlin syndrome 4

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.57

(source)

DANN

Benign

0.55

PhyloP100

0.18

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over