chr16-88804608-A-G

Position:

chr16-88804608-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000301019.9(CDT1):c.292A>G(p.Ile98Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,612,900 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I98T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 3 hom. )

Consequence

CDT1
ENST00000301019.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.14

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 -16 ACMG points.

BP6

Variant 16-88804608-A-G is Benign according to our data. Variant chr16-88804608-A-G is described in ClinVar as [Benign]. Clinvar id is 434672.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 = 0.00387 (589/152244) while in subpopulation AFR AF= 0.0134 (555/41540). AF 95% confidence interval is 0.0124. There are 4 homozygotes in gnomad4. There are 301 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDT1	NM_030928.4 linkuse as main transcript	c.292A>G	p.Ile98Val	missense_variant	2/10	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.292A>G	p.Ile98Val	missense_variant	2/10	1	NM_030928.4	ENSP00000301019	P1
CDT1	ENST00000562747.1 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

587

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.0000735

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00132

AC:

329

AN:

249024

Hom.:

AF XY:

0.000917

AC XY:

124

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000445

AC:

650

AN:

1460656

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

293

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.00387

AC:

589

AN:

152244

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00479

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00151

AC:

183

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	CDT1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 19, 2017

- -

CDT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 14, 2024

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.037

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.25

REVEL

Benign

0.084

Sift

Benign

0.56

Sift4G

Benign

1.0

Polyphen

0.062

Vest4

0.036

MVP

0.56

MPC

0.013

ClinPred

0.0021

GERP RS

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.33

Position offset: -1

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