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GeneBe

16-88803846-C-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_030928.4(CDT1):c.15C>A(p.Arg5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,500,990 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.56
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-88803846-C-A is Benign according to our data. Variant chr16-88803846-C-A is described in ClinVar as [Benign]. Clinvar id is 723696.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.56 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00177 (268/151034) while in subpopulation AFR AF= 0.00599 (248/41420). AF 95% confidence interval is 0.00538. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDT1NM_030928.4 linkuse as main transcriptc.15C>A p.Arg5= synonymous_variant 1/10 ENST00000301019.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDT1ENST00000301019.9 linkuse as main transcriptc.15C>A p.Arg5= synonymous_variant 1/101 NM_030928.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00177
AC:
267
AN:
150926
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00598
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
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:
0.00
Gnomad OTH
AF:
0.00193
GnomAD3 exomes
AF:
0.000307
AC:
56
AN:
182456
Hom.:
1
AF XY:
0.000212
AC XY:
22
AN XY:
103708
show subpopulations
Gnomad AFR exome
AF:
0.00612
Gnomad AMR exome
AF:
0.000106
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000118
Gnomad OTH exome
AF:
0.000231
GnomAD4 exome
AF:
0.000130
AC:
176
AN:
1349956
Hom.:
0
Cov.:
31
AF XY:
0.0000818
AC XY:
55
AN XY:
672438
show subpopulations
Gnomad4 AFR exome
AF:
0.00523
Gnomad4 AMR exome
AF:
0.000213
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000124
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000284
Gnomad4 OTH exome
AF:
0.000369
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00177
AC:
268
AN:
151034
Hom.:
1
Cov.:
32
AF XY:
0.00171
AC XY:
126
AN XY:
73784
show subpopulations
Gnomad4 AFR
AF:
0.00599
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00191
Alfa
AF:
0.00122
Hom.:
0
Bravo
AF:
0.00197

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 12, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
8.9
Dann
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372245967; hg19: chr16-88870254; API