rs587780306

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030928.4(CDT1):c.130A>C(p.Thr44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,427,622 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 22 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 18 hom. )

Consequence

CDT1
NM_030928.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.280

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033073127).

BP6

Variant 16-88803961-A-C is Benign according to our data. Variant chr16-88803961-A-C is described in ClinVar as [Benign]. Clinvar id is 128667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88803961-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00903 (1362/150906) while in subpopulation AFR AF= 0.0305 (1255/41208). AF 95% confidence interval is 0.0291. There are 22 homozygotes in gnomad4. There are 633 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.130A>C	p.Thr44Pro	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.130A>C	p.Thr44Pro	missense_variant	Exon 1 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1356

AN:

150794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00521

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00676

GnomAD3 exomes

AF:

0.000577

AC:

AN:

67570

Hom.:

AF XY:

0.000481

AC XY:

AN XY:

39500

show subpopulations

Gnomad AFR exome

AF:

0.0296

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.000898

AC:

1146

AN:

1276716

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

494

AN XY:

629580

show subpopulations

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.0000472

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00903

AC:

1362

AN:

150906

Hom.:

Cov.:

AF XY:

0.00859

AC XY:

633

AN XY:

73722

show subpopulations

Gnomad4 AFR

AF:

0.0305

Gnomad4 AMR

AF:

0.00520

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.00669

Alfa

AF:

0.00151

Hom.:

ExAC

AF:

0.000560

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 04, 2016

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

0.046

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.53

DEOGEN2

Benign

0.017

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.13

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.23

REVEL

Benign

0.020

Sift

Benign

0.40

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.024

MVP

0.32

MPC

1.6

ClinPred

0.00069

GERP RS

-2.5

Varity_R

0.053

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over