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GeneBe

16-88803942-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030928.4(CDT1):c.111C>T(p.Leu37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,401,470 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

CDT1
NM_030928.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.184
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 -21 ACMG points.

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=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-88803942-C-T is Benign according to our data. Variant chr16-88803942-C-T is described in ClinVar as [Benign]. Clinvar id is 128660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=-0.184 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00109 (165/151272) while in subpopulation SAS AF= 0.00124 (6/4822). AF 95% confidence interval is 0.000719. There are 2 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDT1NM_030928.4 linkuse as main transcriptc.111C>T p.Leu37= synonymous_variant 1/10 ENST00000301019.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDT1ENST00000301019.9 linkuse as main transcriptc.111C>T p.Leu37= synonymous_variant 1/101 NM_030928.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00109
AC:
165
AN:
151170
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000856
Gnomad ASJ
AF:
0.0205
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.000195
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.000901
Gnomad OTH
AF:
0.00193
GnomAD3 exomes
AF:
0.00261
AC:
157
AN:
60082
Hom.:
0
AF XY:
0.00248
AC XY:
88
AN XY:
35470
show subpopulations
Gnomad AFR exome
AF:
0.00149
Gnomad AMR exome
AF:
0.000863
Gnomad ASJ exome
AF:
0.0179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000817
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00150
Gnomad OTH exome
AF:
0.00388
GnomAD4 exome
AF:
0.00122
AC:
1523
AN:
1250198
Hom.:
5
Cov.:
31
AF XY:
0.00122
AC XY:
754
AN XY:
616094
show subpopulations
Gnomad4 AFR exome
AF:
0.000249
Gnomad4 AMR exome
AF:
0.000964
Gnomad4 ASJ exome
AF:
0.0198
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000671
Gnomad4 FIN exome
AF:
0.000361
Gnomad4 NFE exome
AF:
0.000869
Gnomad4 OTH exome
AF:
0.00280
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00109
AC:
165
AN:
151272
Hom.:
2
Cov.:
33
AF XY:
0.00101
AC XY:
75
AN XY:
73936
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000855
Gnomad4 ASJ
AF:
0.0205
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.000195
Gnomad4 NFE
AF:
0.000901
Gnomad4 OTH
AF:
0.00191
Alfa
AF:
0.00166
Hom.:
1
Bravo
AF:
0.00107

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 12, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
4.7
Dann
Benign
0.95
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: rs587780304; hg19: chr16-88870350; COSMIC: COSV56349506; COSMIC: COSV56349506; API