Genetic Variant CDT1:c.933+13C>T (chr16-88806134-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030928.4(CDT1):c.933+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 1,576,550 control chromosomes in the GnomAD database, including 7,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2761 hom., cov: 34)

Exomes 𝑓: 0.065 ( 4962 hom. )

Consequence

CDT1
NM_030928.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -6.47

Publications

4 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 16-88806134-C-T is Benign according to our data. Variant chr16-88806134-C-T is described in ClinVar as Benign. ClinVar VariationId is 261939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030928.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	NM_030928.4	MANE Select	c.933+13C>T		intron	N/A	NP_112190.2	Q9H211

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDT1	ENST00000301019.9	TSL:1 MANE Select	c.933+13C>T	intron	N/A	ENSP00000301019.4	Q9H211
CDT1	ENST00000929785.1		c.933+13C>T	intron	N/A	ENSP00000599844.1
CDT1	ENST00000569140.1	TSL:3	c.201+13C>T	intron	N/A	ENSP00000456926.1	H3BSY1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21235

AN:

152184

Hom.:

2753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0872

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.0841

Gnomad FIN

AF:

0.0377

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0576

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.0847

AC:

16667

AN:

196808

AF XY:

0.0814

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.0559

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.0255

Gnomad FIN exome

AF:

0.0384

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0784

GnomAD4 exome

AF:

0.0646

AC:

91938

AN:

1424248

Hom.:

4962

Cov.:

AF XY:

0.0651

AC XY:

46030

AN XY:

707162

show subpopulations

African (AFR)

AF:

0.359

AC:

11833

AN:

32998

American (AMR)

AF:

0.0620

AC:

2574

AN:

41538

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3811

AN:

25654

East Asian (EAS)

AF:

0.0158

AC:

608

AN:

38602

South Asian (SAS)

AF:

0.0940

AC:

7811

AN:

83090

European-Finnish (FIN)

AF:

0.0353

AC:

1395

AN:

39522

Middle Eastern (MID)

AF:

0.122

AC:

703

AN:

5744

European-Non Finnish (NFE)

AF:

0.0531

AC:

58344

AN:

1097726

Other (OTH)

AF:

0.0818

AC:

4859

AN:

59374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

4462

8924

13387

17849

22311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2338

4676

7014

9352

11690

<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:

0.140

AC:

21278

AN:

152302

Hom.:

2761

Cov.:

AF XY:

0.137

AC XY:

10215

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.343

AC:

14244

AN:

41558

American (AMR)

AF:

0.0870

AC:

1330

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

503

AN:

3470

East Asian (EAS)

AF:

0.0231

AC:

120

AN:

5186

South Asian (SAS)

AF:

0.0837

AC:

404

AN:

4826

European-Finnish (FIN)

AF:

0.0377

AC:

400

AN:

10624

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0576

AC:

3916

AN:

68026

Other (OTH)

AF:

0.133

AC:

282

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

843

1687

2530

3374

4217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.106

Hom.:

311

Bravo

AF:

0.153

Asia WGS

AF:

0.0650

AC:

226

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.012

(source)

DANN

Benign

0.71

PhyloP100

-6.5

PromoterAI

-0.0095

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over