rs3218721

Positions:

• chr16-88808247-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030928.4(CDT1):​c.1610C>T​(p.Ala537Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,601,962 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.019 (79 hom., cov: 35)
  • Exomes 𝑓: 0.0026 (81 hom.)
• Consequence: CDT1 NM_030928.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.240

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028153956).
• BP6: Variant 16-88808247-C-T is Benign according to our data. Variant chr16-88808247-C-T is described in ClinVar as [Benign]. Clinvar id is 128674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88808247-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDT1	NM_030928.4	c.1610C>T	p.Ala537Val	missense_variant	10/10	ENST00000301019.9	NP_112190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9	c.1610C>T	p.Ala537Val	missense_variant	10/10	1	NM_030928.4	ENSP00000301019.4

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2851 AN: 152260 Hom.: 76 Cov.: 35

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00948

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00612 AC: 1379 AN: 225488 Hom.: 38 AF XY: 0.00547 AC XY: 669 AN XY: 122400

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000199

Gnomad OTH exome AF: 0.00321

GnomAD4 exome AF: 0.00258 AC: 3745 AN: 1449584 Hom.: 81 Cov.: 34 AF XY: 0.00256 AC XY: 1846 AN XY: 720094

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.00459

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000940

Gnomad4 OTH exome AF: 0.00624

GnomAD4 genome AF: 0.0188 AC: 2870 AN: 152378 Hom.: 79 Cov.: 35 AF XY: 0.0187 AC XY: 1393 AN XY: 74522

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.00947

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00622 Hom.: 24

Bravo AF: 0.0221

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0617 AC: 270

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00722 AC: 871

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 04, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 02, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.087
Sift	Benign	0.10	T
Sift4G	Benign	0.22	T
Polyphen		0.0050	B
Vest4		0.066
MVP		0.64
MPC		0.013
ClinPred		0.0028	T
GERP RS		-0.092
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.042
gMVP		0.23

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

Other links and lift over

dbSNP: rs3218721; hg19: chr16-88874655;