rs1834065

Variant names:

• chr16-88805500-A-G
• rs1834065
• NM_030928.4:c.549A>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.549A>G​(p.Gly183Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,612,704 control chromosomes in the GnomAD database, including 8,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2318 hom., cov: 34)
  • Exomes 𝑓: 0.072 (5752 hom.)
• Consequence: CDT1 NM_030928.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.417
• Publications: 11 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=-0.59).
• BP6: Variant 16-88805500-A-G is Benign according to our data. Variant chr16-88805500-A-G is described in ClinVar as Benign. ClinVar VariationId is 128679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.417 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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.549A>G	p.Gly183Gly	synonymous	Exon 4 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.549A>G	p.Gly183Gly	synonymous	Exon 4 of 10	ENSP00000301019.4
	CDT1	ENST00000562747.1	TSL:2	n.255A>G		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20310 AN: 152054 Hom.: 2313 Cov.: 34

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.0837 AC: 20894 AN: 249580 AF XY: 0.0828

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.0512

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.00285

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0675

Gnomad OTH exome AF: 0.0806

GnomAD4 exome AF: 0.0724 AC: 105781 AN: 1460532 Hom.: 5752 Cov.: 32 AF XY: 0.0739 AC XY: 53713 AN XY: 726586

African (AFR) AF: 0.322 AC: 10786 AN: 33476

American (AMR) AF: 0.0573 AC: 2561 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4362 AN: 26124

East Asian (EAS) AF: 0.00237 AC: 94 AN: 39694

South Asian (SAS) AF: 0.124 AC: 10665 AN: 86256

European-Finnish (FIN) AF: 0.0218 AC: 1140 AN: 52188

Middle Eastern (MID) AF: 0.130 AC: 750 AN: 5768

European-Non Finnish (NFE) AF: 0.0632 AC: 70304 AN: 1111932

Other (OTH) AF: 0.0848 AC: 5119 AN: 60372

GnomAD4 genome AF: 0.134 AC: 20339 AN: 152172 Hom.: 2318 Cov.: 34 AF XY: 0.130 AC XY: 9681 AN XY: 74406

African (AFR) AF: 0.310 AC: 12867 AN: 41494

American (AMR) AF: 0.0821 AC: 1257 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3470

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5174

South Asian (SAS) AF: 0.110 AC: 530 AN: 4830

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10610

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4522 AN: 67970

Other (OTH) AF: 0.122 AC: 258 AN: 2114

Alfa AF: 0.0960 Hom.: 1663

Bravo AF: 0.146

Asia WGS AF: 0.0640 AC: 221 AN: 3478

EpiCase AF: 0.0732

EpiControl AF: 0.0758

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	-0.59
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		0.42
PromoterAI		-0.022	Neutral
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: rs1834065; hg19: chr16-88871908; COSMIC: COSV56347983; COSMIC: COSV56347983;