16-88804016-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030928.4(CDT1):c.185C>T(p.Ala62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,463,926 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. A62T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0073 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 76 hom. )

Consequence

CDT1
NM_030928.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.86

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029655993).

BP6

Variant 16-88804016-C-T is Benign according to our data. Variant chr16-88804016-C-T is described in ClinVar as Benign. ClinVar VariationId is 434671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00725 (1102/151980) while in subpopulation EAS AF = 0.0199 (103/5168). AF 95% confidence interval is 0.0168. There are 34 homozygotes in GnomAd4. There are 793 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.185C>T	p.Ala62Val	missense_variant	Exon 1 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.185C>T	p.Ala62Val	missense_variant	Exon 1 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1101

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.0201

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00670

AC:

522

AN:

77870

AF XY:

0.00527

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00684

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.0218

Gnomad FIN exome

AF:

0.0551

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.00390

GnomAD4 exome

AF:

0.00309

AC:

4055

AN:

1311946

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

1921

AN XY:

647274

show subpopulations

African (AFR)

AF:

0.0000764

AC:

AN:

26172

American (AMR)

AF:

0.00737

AC:

187

AN:

25366

Ashkenazi Jewish (ASJ)

AF:

0.00132

AC:

AN:

22744

East Asian (EAS)

AF:

0.0381

AC:

1105

AN:

29020

South Asian (SAS)

AF:

0.00217

AC:

155

AN:

71590

European-Finnish (FIN)

AF:

0.0500

AC:

1611

AN:

32206

Middle Eastern (MID)

AF:

0.000774

AC:

AN:

3874

European-Non Finnish (NFE)

AF:

0.000718

AC:

752

AN:

1046812

Other (OTH)

AF:

0.00388

AC:

210

AN:

54162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

185

369

554

738

923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00725

AC:

1102

AN:

151980

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

793

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41538

American (AMR)

AF:

0.00877

AC:

134

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3462

East Asian (EAS)

AF:

0.0199

AC:

103

AN:

5168

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0685

AC:

724

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00162

AC:

110

AN:

67822

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00230

Hom.:

Bravo

AF:

0.00309

ExAC

AF:

0.00212

AC:

Asia WGS

AF:

0.0130

AC:

AN:

3332

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not specified

Benign:1

Aug 23, 2017

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.9

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.93

REVEL

Benign

0.016

Sift

Benign

0.28

Sift4G

Benign

0.30

Polyphen

0.063

Vest4

0.081

MVP

0.79

MPC

1.2

ClinPred

0.019

GERP RS

1.7

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.039

gMVP

0.16

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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