16-88807382-C-T

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.1377C>T(p.Arg459Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,612,690 control chromosomes in the GnomAD database, including 2,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 267 hom., cov: 34)

Exomes 𝑓: 0.054 ( 2567 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.34

Publications

14 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=-0.64).

BP6

Variant 16-88807382-C-T is Benign according to our data. Variant chr16-88807382-C-T is described in ClinVar as Benign. ClinVar VariationId is 128669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.067 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.1377C>T	p.Arg459Arg	synonymous_variant	Exon 9 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.1377C>T	p.Arg459Arg	synonymous_variant	Exon 9 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211
CDT1	ENST00000569140.1 link	c.*40C>T		downstream_gene_variant		3		ENSP00000456926.1		H3BSY1

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8585

AN:

152240

Hom.:

267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0558

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0554

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.0246

Gnomad SAS

AF:

0.0734

Gnomad FIN

AF:

0.0378

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0566

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0555

AC:

13781

AN:

248160

AF XY:

0.0577

show subpopulations

Gnomad AFR exome

AF:

0.0511

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.0249

Gnomad FIN exome

AF:

0.0355

Gnomad NFE exome

AF:

0.0565

Gnomad OTH exome

AF:

0.0620

GnomAD4 exome

AF:

0.0543

AC:

79333

AN:

1460332

Hom.:

2567

Cov.:

AF XY:

0.0559

AC XY:

40607

AN XY:

726484

show subpopulations

African (AFR)

AF:

0.0572

AC:

1916

AN:

33474

American (AMR)

AF:

0.0414

AC:

1853

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3619

AN:

26118

East Asian (EAS)

AF:

0.0184

AC:

730

AN:

39696

South Asian (SAS)

AF:

0.0827

AC:

7130

AN:

86252

European-Finnish (FIN)

AF:

0.0347

AC:

1805

AN:

52056

Middle Eastern (MID)

AF:

0.103

AC:

590

AN:

5748

European-Non Finnish (NFE)

AF:

0.0523

AC:

58150

AN:

1111922

Other (OTH)

AF:

0.0587

AC:

3540

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5121

10242

15362

20483

25604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2176

4352

6528

8704

10880

<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:

0.0564

AC:

8593

AN:

152358

Hom.:

267

Cov.:

AF XY:

0.0565

AC XY:

4209

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0560

AC:

2328

AN:

41584

American (AMR)

AF:

0.0553

AC:

847

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

472

AN:

3468

East Asian (EAS)

AF:

0.0245

AC:

127

AN:

5194

South Asian (SAS)

AF:

0.0733

AC:

354

AN:

4830

European-Finnish (FIN)

AF:

0.0378

AC:

401

AN:

10622

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0566

AC:

3848

AN:

68026

Other (OTH)

AF:

0.0676

AC:

143

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

426

851

1277

1702

2128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0507

Hom.:

136

Bravo

AF:

0.0564

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

EpiCase

AF:

0.0632

EpiControl

AF:

0.0653

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 09, 2018

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.3

(source)

DANN

Benign

0.82

PhyloP100

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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