16-88805737-T-C

Variant names:

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.700T>C(p.Cys234Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,613,060 control chromosomes in the GnomAD database, including 805,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C234Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 1.0 ( 76087 hom., cov: 33)

Exomes 𝑓: 1.0 ( 729112 hom. )

Consequence

CDT1
NM_030928.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.10

Publications

33 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 (MetaRNN=6.5709366E-7).

BP6

Variant 16-88805737-T-C is Benign according to our data. Variant chr16-88805737-T-C is described in ClinVar as Benign. ClinVar VariationId is 128680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.700T>C	p.Cys234Arg	missense	Exon 5 of 10	NP_112190.2	Q9H211

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDT1	ENST00000301019.9	TSL:1 MANE Select	c.700T>C	p.Cys234Arg	missense	Exon 5 of 10	ENSP00000301019.4	Q9H211
CDT1	ENST00000929785.1		c.700T>C	p.Cys234Arg	missense	Exon 5 of 10	ENSP00000599844.1
CDT1	ENST00000562747.1	TSL:2	n.406T>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

152138

AN:

152220

Hom.:

76028

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

1.00

GnomAD2 exomes

AF:

0.999

AC:

250080

AN:

250218

AF XY:

0.999

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1459471

AN:

1460722

Hom.:

729112

Cov.:

AF XY:

0.999

AC XY:

726049

AN XY:

726644

show subpopulations

African (AFR)

AF:

1.00

AC:

33471

AN:

33480

American (AMR)

AF:

1.00

AC:

44718

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26132

AN:

26132

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39698

South Asian (SAS)

AF:

1.00

AC:

86258

AN:

86258

European-Finnish (FIN)

AF:

1.00

AC:

52294

AN:

52296

Middle Eastern (MID)

AF:

1.00

AC:

5764

AN:

5764

European-Non Finnish (NFE)

AF:

0.999

AC:

1110784

AN:

1111994

Other (OTH)

AF:

1.00

AC:

60352

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

156

233

311

389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21672

43344

65016

86688

108360

<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:

0.999

AC:

152256

AN:

152338

Hom.:

76087

Cov.:

AF XY:

1.00

AC XY:

74456

AN XY:

74490

show subpopulations

African (AFR)

AF:

1.00

AC:

41577

AN:

41584

American (AMR)

AF:

1.00

AC:

15305

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5174

AN:

5174

South Asian (SAS)

AF:

1.00

AC:

4832

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10617

AN:

10618

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67963

AN:

68034

Other (OTH)

AF:

1.00

AC:

2110

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.999

Hom.:

120317

Bravo

AF:

0.999

TwinsUK

AF:

0.999

AC:

3705

ALSPAC

AF:

0.999

AC:

3851

ESP6500AA

AF:

1.00

AC:

4395

ESP6500EA

AF:

0.999

AC:

8595

ExAC

AF:

0.999

AC:

121175

Asia WGS

AF:

0.999

AC:

3472

AN:

3474

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Meier-Gorlin syndrome 4 (3)

not provided (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.026

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.0056

MetaRNN

Benign

6.6e-7

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.5

PhyloP100

1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

4.3

REVEL

Benign

0.088

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.016

MPC

0.013

ClinPred

0.0013

GERP RS

3.8

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.59

Mutation Taster

=98/2

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