16-88806134-C-T

Variant names:

• chr16-88806134-C-T
• rs3218722
• NM_030928.4:c.933+13C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030928.4(CDT1):​c.933+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 1,576,550 control chromosomes in the GnomAD database, including 7,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2761 hom., cov: 34)
  • Exomes 𝑓: 0.065 (4962 hom.)
• Consequence: CDT1 NM_030928.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.47
• Publications: 4 publications found

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]

CDT1 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Meier-Gorlin syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-88806134-C-T is Benign according to our data. Variant chr16-88806134-C-T is described in ClinVar as [Benign]. Clinvar id is 261939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4	c.933+13C>T		intron_variant	Intron 6 of 9	ENST00000301019.9	NP_112190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9	c.933+13C>T		intron_variant	Intron 6 of 9	1	NM_030928.4	ENSP00000301019.4
CDT1	ENST00000562747.1	n.652C>T		non_coding_transcript_exon_variant	Exon 5 of 5	2
CDT1	ENST00000569140.1	c.201+13C>T		intron_variant	Intron 2 of 4	3		ENSP00000456926.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21235 AN: 152184 Hom.: 2753 Cov.: 34

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.0847 AC: 16667 AN: 196808 AF XY: 0.0814

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.0559

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0255

Gnomad FIN exome AF: 0.0384

Gnomad NFE exome AF: 0.0610

Gnomad OTH exome AF: 0.0784

GnomAD4 exome AF: 0.0646 AC: 91938 AN: 1424248 Hom.: 4962 Cov.: 34 AF XY: 0.0651 AC XY: 46030 AN XY: 707162

African (AFR) AF: 0.359 AC: 11833 AN: 32998

American (AMR) AF: 0.0620 AC: 2574 AN: 41538

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3811 AN: 25654

East Asian (EAS) AF: 0.0158 AC: 608 AN: 38602

South Asian (SAS) AF: 0.0940 AC: 7811 AN: 83090

European-Finnish (FIN) AF: 0.0353 AC: 1395 AN: 39522

Middle Eastern (MID) AF: 0.122 AC: 703 AN: 5744

European-Non Finnish (NFE) AF: 0.0531 AC: 58344 AN: 1097726

Other (OTH) AF: 0.0818 AC: 4859 AN: 59374

GnomAD4 genome AF: 0.140 AC: 21278 AN: 152302 Hom.: 2761 Cov.: 34 AF XY: 0.137 AC XY: 10215 AN XY: 74472

African (AFR) AF: 0.343 AC: 14244 AN: 41558

American (AMR) AF: 0.0870 AC: 1330 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3470

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5186

South Asian (SAS) AF: 0.0837 AC: 404 AN: 4826

European-Finnish (FIN) AF: 0.0377 AC: 400 AN: 10624

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3916 AN: 68026

Other (OTH) AF: 0.133 AC: 282 AN: 2116

Alfa AF: 0.106 Hom.: 311

Bravo AF: 0.153

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.012
DANN	Benign	0.71
PhyloP100		-6.5
PromoterAI		-0.0095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3218722; hg19: chr16-88872542;