Variant 16-88804016-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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=0.0029655993).

BP6

Variant 16-88804016-C-T is Benign according to our data. Variant chr16-88804016-C-T is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDT1	NM_030928.4 linkuse as main transcript	c.185C>T	p.Ala62Val	missense_variant	1/10	ENST00000301019.9	NP_112190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9 linkuse as main transcript	c.185C>T	p.Ala62Val	missense_variant	1/10	1	NM_030928.4	ENSP00000301019	P1

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

GnomAD3 exomes

AF:

0.00670

AC:

522

AN:

77870

Hom.:

AF XY:

0.00527

AC XY:

237

AN XY:

44988

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 SAS exome

AF:

0.00193

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

Gnomad4 AFR exome

AF:

0.0000764

Gnomad4 AMR exome

AF:

0.00737

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.0381

Gnomad4 SAS exome

AF:

0.00217

Gnomad4 FIN exome

AF:

0.0500

Gnomad4 NFE exome

AF:

0.000718

Gnomad4 OTH exome

AF:

0.00388

GnomAD4 genome

AF:

0.00725

AC:

1102

AN:

151980

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

793

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00877

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00237

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 23, 2017

- -

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

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

MutationTaster

Benign

1.0

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.039

gMVP

0.16

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

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