16-88808284-G-C

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.*6G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,579,418 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 35)
  • Exomes 𝑓: 0.0022 (60 hom.)
• Consequence: CDT1 NM_030928.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.423

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 (BayesDel_noAF=-0.81).
• BP6: Variant 16-88808284-G-C is Benign according to our data. Variant chr16-88808284-G-C is described in ClinVar as [Benign]. Clinvar id is 128663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDT1	NM_030928.4	c.*6G>C		3_prime_UTR_variant	10/10	ENST00000301019.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDT1	ENST00000301019.9	c.*6G>C		3_prime_UTR_variant	10/10	1	NM_030928.4	P1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2403 AN: 152240 Hom.: 57 Cov.: 35

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00535 AC: 1018 AN: 190250 Hom.: 25 AF XY: 0.00498 AC XY: 511 AN XY: 102588

Gnomad AFR exome AF: 0.0575

Gnomad AMR exome AF: 0.00262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00222 AC: 3165 AN: 1427060 Hom.: 60 Cov.: 34 AF XY: 0.00223 AC XY: 1577 AN XY: 706868

Gnomad4 AFR exome AF: 0.0546

Gnomad4 AMR exome AF: 0.00356

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000667

Gnomad4 OTH exome AF: 0.00524

GnomAD4 genome AF: 0.0159 AC: 2420 AN: 152358 Hom.: 59 Cov.: 35 AF XY: 0.0159 AC XY: 1184 AN XY: 74516

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.00718

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00175 Hom.: 2

Bravo AF: 0.0186

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 02, 2013

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.41
Dann	Benign	0.50

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: rs3218723; hg19: chr16-88874692;