Variant rs475667 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030928.4(CDT1):c.243T>C(p.Ser81Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,612,354 control chromosomes in the GnomAD database, including 6,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1129 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5692 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.04

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-88804559-T-C is Benign according to our data. Variant chr16-88804559-T-C is described in ClinVar as [Benign]. Clinvar id is 128675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88804559-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.243T>C	p.Ser81Ser	synonymous_variant	2/10	ENST00000301019.9	NP_112190.2	Q9H211

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9 link	c.243T>C	p.Ser81Ser	synonymous_variant	2/10	1	NM_030928.4	ENSP00000301019.4		Q9H211

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17051

AN:

152052

Hom.:

1127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0774

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.0968

AC:

24114

AN:

249178

Hom.:

1379

AF XY:

0.0968

AC XY:

13073

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0805

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0819

AC:

119605

AN:

1460184

Hom.:

5692

Cov.:

AF XY:

0.0829

AC XY:

60204

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.0969

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0729

Gnomad4 OTH exome

AF:

0.0956

GnomAD4 genome

AF:

0.112

AC:

17078

AN:

152170

Hom.:

1129

Cov.:

AF XY:

0.111

AC XY:

8248

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0775

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.0940

Hom.:

854

Bravo

AF:

0.121

Asia WGS

AF:

0.175

AC:

609

AN:

3478

EpiCase

AF:

0.0888

EpiControl

AF:

0.0883

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.42

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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