rs1834065

chr16-88805500-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_030928.4(CDT1):c.549A>G(p.Gly183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,612,704 control chromosomes in the GnomAD database, including 8,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2318 hom., cov: 34)
  • Exomes 𝑓: 0.072 (5752 hom.)
• Consequence: CDT1 NM_030928.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.417

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-88805500-A-G is Benign according to our data. Variant chr16-88805500-A-G is described in ClinVar as [Benign]. Clinvar id is 128679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88805500-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.417 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDT1	NM_030928.4	c.549A>G	p.Gly183=	synonymous_variant	4/10	ENST00000301019.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDT1	ENST00000301019.9	c.549A>G	p.Gly183=	synonymous_variant	4/10	1	NM_030928.4	P1
CDT1	ENST00000562747.1	n.255A>G		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20310 AN: 152054 Hom.: 2313 Cov.: 34

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.0837 AC: 20894 AN: 249580 Hom.: 1590 AF XY: 0.0828 AC XY: 11221 AN XY: 135550

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.0512

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.00285

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0675

Gnomad OTH exome AF: 0.0806

GnomAD4 exome AF: 0.0724 AC: 105781 AN: 1460532 Hom.: 5752 Cov.: 32 AF XY: 0.0739 AC XY: 53713 AN XY: 726586

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.0573

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00237

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0218

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.0848

GnomAD4 genome AF: 0.134 AC: 20339 AN: 152172 Hom.: 2318 Cov.: 34 AF XY: 0.130 AC XY: 9681 AN XY: 74406

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0947 Hom.: 1216

Bravo AF: 0.146

Asia WGS AF: 0.0640 AC: 221 AN: 3478

EpiCase AF: 0.0732

EpiControl AF: 0.0758

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	6.8
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1834065; hg19: chr16-88871908; COSMIC: COSV56347983; COSMIC: COSV56347983;