chr16-88808137-G-T

Variant names:

• chr16-88808137-G-T
• rs3218720
• NM_030928.4:c.1500G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_030928.4(CDT1):​c.1500G>T​(p.Leu500Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,612,660 control chromosomes in the GnomAD database, including 842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (426 hom., cov: 34)
  • Exomes 𝑓: 0.0042 (416 hom.)
• Consequence: CDT1 NM_030928.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0930
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-88808137-G-T is Benign according to our data. Variant chr16-88808137-G-T is described in ClinVar as Benign. ClinVar VariationId is 128670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.093 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030928.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	NM_030928.4	MANE Select	c.1500G>T	p.Leu500Leu	synonymous	Exon 10 of 10	NP_112190.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	ENST00000301019.9	TSL:1 MANE Select	c.1500G>T	p.Leu500Leu	synonymous	Exon 10 of 10	ENSP00000301019.4
	CDT1	ENST00000929785.1		c.1521G>T	p.Leu507Leu	synonymous	Exon 10 of 10	ENSP00000599844.1

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6175 AN: 152162 Hom.: 426 Cov.: 34

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0296

GnomAD2 exomes AF: 0.0108 AC: 2664 AN: 247326 AF XY: 0.00771

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00413

GnomAD4 exome AF: 0.00420 AC: 6134 AN: 1460380 Hom.: 416 Cov.: 31 AF XY: 0.00359 AC XY: 2606 AN XY: 726474

African (AFR) AF: 0.147 AC: 4916 AN: 33468

American (AMR) AF: 0.00839 AC: 375 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86192

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52184

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.000244 AC: 271 AN: 1111902

Other (OTH) AF: 0.00880 AC: 531 AN: 60368

GnomAD4 genome AF: 0.0406 AC: 6179 AN: 152280 Hom.: 426 Cov.: 34 AF XY: 0.0389 AC XY: 2899 AN XY: 74466

African (AFR) AF: 0.142 AC: 5894 AN: 41524

American (AMR) AF: 0.0124 AC: 190 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68020

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0166 Hom.: 76

Bravo AF: 0.0463

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		0.093
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3218720; hg19: chr16-88874545;