NM_030928.4:c.915T>C

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.915T>C(p.His305His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,598,186 control chromosomes in the GnomAD database, including 508,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54038 hom., cov: 35)

Exomes 𝑓: 0.79 ( 454843 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.92

Publications

27 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=-0.93).

BP6

Variant 16-88806103-T-C is Benign according to our data. Variant chr16-88806103-T-C is described in ClinVar as Benign. ClinVar VariationId is 128683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.915T>C	p.His305His	synonymous_variant	Exon 6 of 10	ENST00000301019.9	NP_112190.2	Q9H211

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDT1	ENST00000301019.9 link	c.915T>C	p.His305His	synonymous_variant	Exon 6 of 10	1	NM_030928.4	ENSP00000301019.4	Q9H211
CDT1	ENST00000569140.1 link	c.183T>C	p.His61His	synonymous_variant	Exon 2 of 5	3		ENSP00000456926.1	H3BSY1
CDT1	ENST00000562747.1 link	n.621T>C		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.839

AC:

127616

AN:

152128

Hom.:

53983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.858

Gnomad AMR

AF:

0.769

Gnomad ASJ

AF:

0.868

Gnomad EAS

AF:

0.899

Gnomad SAS

AF:

0.857

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.788

Gnomad OTH

AF:

0.832

GnomAD2 exomes

AF:

0.801

AC:

181848

AN:

227080

AF XY:

0.804

show subpopulations

Gnomad AFR exome

AF:

0.962

Gnomad AMR exome

AF:

0.679

Gnomad ASJ exome

AF:

0.866

Gnomad EAS exome

AF:

0.896

Gnomad FIN exome

AF:

0.741

Gnomad NFE exome

AF:

0.790

Gnomad OTH exome

AF:

0.801

GnomAD4 exome

AF:

0.792

AC:

1144914

AN:

1445940

Hom.:

454843

Cov.:

AF XY:

0.794

AC XY:

570749

AN XY:

718954

show subpopulations

African (AFR)

AF:

0.968

AC:

32321

AN:

33388

American (AMR)

AF:

0.694

AC:

30281

AN:

43606

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

22537

AN:

25952

East Asian (EAS)

AF:

0.888

AC:

35012

AN:

39408

South Asian (SAS)

AF:

0.846

AC:

71929

AN:

85046

European-Finnish (FIN)

AF:

0.753

AC:

33338

AN:

44272

Middle Eastern (MID)

AF:

0.846

AC:

4867

AN:

5752

European-Non Finnish (NFE)

AF:

0.781

AC:

866181

AN:

1108496

Other (OTH)

AF:

0.807

AC:

48448

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

14136

28272

42409

56545

70681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20574

41148

61722

82296

102870

<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:

0.839

AC:

127726

AN:

152246

Hom.:

54038

Cov.:

AF XY:

0.835

AC XY:

62185

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.959

AC:

39866

AN:

41582

American (AMR)

AF:

0.769

AC:

11762

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

3013

AN:

3472

East Asian (EAS)

AF:

0.899

AC:

4655

AN:

5178

South Asian (SAS)

AF:

0.859

AC:

4145

AN:

4828

European-Finnish (FIN)

AF:

0.750

AC:

7936

AN:

10582

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.788

AC:

53559

AN:

67988

Other (OTH)

AF:

0.831

AC:

1756

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1085

2170

3256

4341

5426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.808

Hom.:

87922

Bravo

AF:

0.844

Asia WGS

AF:

0.869

AC:

3023

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

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

- -

Meier-Gorlin syndrome 4

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.014

(source)

DANN

Benign

0.39

PhyloP100

-4.9

PromoterAI

0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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