rs146199695

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1472G>A(p.Ser491Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,612,922 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 34)

Exomes 𝑓: 0.00062 ( 8 hom. )

Consequence

CDT1
NM_030928.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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=0.0040723085).

BP6

Variant 16-88807477-G-A is Benign according to our data. Variant chr16-88807477-G-A is described in ClinVar as Benign. ClinVar VariationId is 434678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00534 (814/152344) while in subpopulation AFR AF = 0.0186 (774/41580). AF 95% confidence interval is 0.0175. There are 7 homozygotes in GnomAd4. There are 396 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.1472G>A	p.Ser491Asn	missense_variant	Exon 9 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.1472G>A	p.Ser491Asn	missense_variant	Exon 9 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211
CDT1	ENST00000569140.1 link	c.*135G>A		downstream_gene_variant		3		ENSP00000456926.1		H3BSY1

Frequencies

GnomAD3 genomes

AF:

0.00533

AC:

812

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00180

AC:

448

AN:

248726

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000447

Gnomad OTH exome

AF:

0.000658

GnomAD4 exome

AF:

0.000624

AC:

911

AN:

1460578

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

400

AN XY:

726588

show subpopulations

African (AFR)

AF:

0.0217

AC:

726

AN:

33468

American (AMR)

AF:

0.00165

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52512

Middle Eastern (MID)

AF:

0.00107

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1111840

Other (OTH)

AF:

0.00133

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00534

AC:

814

AN:

152344

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

396

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0186

AC:

774

AN:

41580

American (AMR)

AF:

0.00131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68022

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

131

175

219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00293

Hom.:

Bravo

AF:

0.00646

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00200

AC:

242

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 19, 2017

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CDT1-related disorder

Benign:1

Aug 14, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.17

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.27

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.80

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

REVEL

Benign

0.056

Sift

Benign

0.071

Sift4G

Benign

0.17

Polyphen

0.0030

Vest4

0.25

MVP

0.73

MPC

0.013

ClinPred

0.0056

GERP RS

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.33

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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