Variant rs572275 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.1587C>G(p.Leu529=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,607,606 control chromosomes in the GnomAD database, including 129,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L529L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.48 ( 19477 hom., cov: 35)

Exomes 𝑓: 0.38 ( 110035 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.176

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=-0.75).

BP6

Variant 16-88808224-C-G is Benign according to our data. Variant chr16-88808224-C-G is described in ClinVar as [Benign]. Clinvar id is 128673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88808224-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.176 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDT1	NM_030928.4 linkuse as main transcript	c.1587C>G	p.Leu529=	synonymous_variant	10/10	ENST00000301019.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDT1	ENST00000301019.9 linkuse as main transcript	c.1587C>G	p.Leu529=	synonymous_variant	10/10	1	NM_030928.4	P1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73391

AN:

152086

Hom.:

19443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.428

AC:

102108

AN:

238566

Hom.:

23309

AF XY:

0.420

AC XY:

54425

AN XY:

129654

show subpopulations

Gnomad AFR exome

AF:

0.706

Gnomad AMR exome

AF:

0.424

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.692

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.379

AC:

551513

AN:

1455400

Hom.:

110035

Cov.:

AF XY:

0.379

AC XY:

274565

AN XY:

723554

show subpopulations

Gnomad4 AFR exome

AF:

0.719

Gnomad4 AMR exome

AF:

0.434

Gnomad4 ASJ exome

AF:

0.519

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.483

AC:

73471

AN:

152206

Hom.:

19477

Cov.:

AF XY:

0.481

AC XY:

35764

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.700

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.519

Gnomad4 EAS

AF:

0.694

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.361

Hom.:

3147

Bravo

AF:

0.505

Asia WGS

AF:

0.531

AC:

1850

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Meier-Gorlin syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.57

DANN

Benign

0.55

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