rs3218730

Variant names:

• chr16-88807382-C-T
• rs3218730
• NM_030928.4:c.1377C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88807382-C-T
• chr16-88807382-C-A
• chr16-88807382-C-G

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.1377C>T​(p.Arg459Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,612,690 control chromosomes in the GnomAD database, including 2,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (267 hom., cov: 34)
  • Exomes 𝑓: 0.054 (2567 hom.)
• Consequence: CDT1 NM_030928.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.34
• Publications: 14 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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=-0.64).
• BP6: Variant 16-88807382-C-T is Benign according to our data. Variant chr16-88807382-C-T is described in ClinVar as Benign. ClinVar VariationId is 128669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.067 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	NM_030928.4	MANE Select	c.1377C>T	p.Arg459Arg	synonymous	Exon 9 of 10	NP_112190.2	Q9H211

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	ENST00000301019.9	TSL:1 MANE Select	c.1377C>T	p.Arg459Arg	synonymous	Exon 9 of 10	ENSP00000301019.4	Q9H211
	CDT1	ENST00000929785.1		c.1377C>T	p.Arg459Arg	synonymous	Exon 9 of 10	ENSP00000599844.1
	CDT1	ENST00000569140.1	TSL:3	c.*40C>T		downstream_gene	N/A	ENSP00000456926.1	H3BSY1

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8585 AN: 152240 Hom.: 267 Cov.: 34

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0684

GnomAD2 exomes AF: 0.0555 AC: 13781 AN: 248160 AF XY: 0.0577

Gnomad AFR exome AF: 0.0511

Gnomad AMR exome AF: 0.0370

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.0249

Gnomad FIN exome AF: 0.0355

Gnomad NFE exome AF: 0.0565

Gnomad OTH exome AF: 0.0620

GnomAD4 exome AF: 0.0543 AC: 79333 AN: 1460332 Hom.: 2567 Cov.: 33 AF XY: 0.0559 AC XY: 40607 AN XY: 726484

African (AFR) AF: 0.0572 AC: 1916 AN: 33474

American (AMR) AF: 0.0414 AC: 1853 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3619 AN: 26118

East Asian (EAS) AF: 0.0184 AC: 730 AN: 39696

South Asian (SAS) AF: 0.0827 AC: 7130 AN: 86252

European-Finnish (FIN) AF: 0.0347 AC: 1805 AN: 52056

Middle Eastern (MID) AF: 0.103 AC: 590 AN: 5748

European-Non Finnish (NFE) AF: 0.0523 AC: 58150 AN: 1111922

Other (OTH) AF: 0.0587 AC: 3540 AN: 60356

GnomAD4 genome AF: 0.0564 AC: 8593 AN: 152358 Hom.: 267 Cov.: 34 AF XY: 0.0565 AC XY: 4209 AN XY: 74510

African (AFR) AF: 0.0560 AC: 2328 AN: 41584

American (AMR) AF: 0.0553 AC: 847 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5194

South Asian (SAS) AF: 0.0733 AC: 354 AN: 4830

European-Finnish (FIN) AF: 0.0378 AC: 401 AN: 10622

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3848 AN: 68026

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0507 Hom.: 136

Bravo AF: 0.0564

Asia WGS AF: 0.0440 AC: 154 AN: 3478

EpiCase AF: 0.0632

EpiControl AF: 0.0653

ClinVar

ClinVar submissions

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	-0.64
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-3.3
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: rs3218730; hg19: chr16-88873790;