rs475667

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.243T>C(p.Ser81Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,612,354 control chromosomes in the GnomAD database, including 6,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1129 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5692 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.04

Publications

16 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=-0.58).

BP6

Variant 16-88804559-T-C is Benign according to our data. Variant chr16-88804559-T-C is described in ClinVar as Benign. ClinVar VariationId is 128675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.243T>C	p.Ser81Ser	synonymous_variant	Exon 2 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.243T>C	p.Ser81Ser	synonymous_variant	Exon 2 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211
CDT1	ENST00000562747.1 link	n.-52T>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17051

AN:

152052

Hom.:

1127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0774

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.0968

AC:

24114

AN:

249178

AF XY:

0.0968

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0805

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0819

AC:

119605

AN:

1460184

Hom.:

5692

Cov.:

AF XY:

0.0829

AC XY:

60204

AN XY:

726288

show subpopulations

African (AFR)

AF:

0.184

AC:

6145

AN:

33468

American (AMR)

AF:

0.0969

AC:

4326

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

3461

AN:

26078

East Asian (EAS)

AF:

0.169

AC:

6714

AN:

39682

South Asian (SAS)

AF:

0.104

AC:

8985

AN:

86140

European-Finnish (FIN)

AF:

0.0438

AC:

2299

AN:

52502

Middle Eastern (MID)

AF:

0.147

AC:

848

AN:

5762

European-Non Finnish (NFE)

AF:

0.0729

AC:

81060

AN:

1111562

Other (OTH)

AF:

0.0956

AC:

5767

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6340

12679

19019

25358

31698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3110

6220

9330

12440

15550

<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:

0.112

AC:

17078

AN:

152170

Hom.:

1129

Cov.:

AF XY:

0.111

AC XY:

8248

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.177

AC:

7355

AN:

41482

American (AMR)

AF:

0.121

AC:

1855

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

470

AN:

3468

East Asian (EAS)

AF:

0.155

AC:

804

AN:

5182

South Asian (SAS)

AF:

0.106

AC:

509

AN:

4822

European-Finnish (FIN)

AF:

0.0387

AC:

410

AN:

10606

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0775

AC:

5270

AN:

68014

Other (OTH)

AF:

0.129

AC:

271

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

780

1559

2339

3118

3898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.0951

Hom.:

1196

Bravo

AF:

0.121

Asia WGS

AF:

0.175

AC:

609

AN:

3478

EpiCase

AF:

0.0888

EpiControl

AF:

0.0883

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

- -

Jul 09, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.42

(source)

DANN

Benign

0.85

PhyloP100

-3.0

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

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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