chr16-88805775-C-T

Variant names:

• chr16-88805775-C-T
• rs200892812
• NM_030928.4:c.738C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030928.4(CDT1):​c.738C>T​(p.Ser246Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,160 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00096 (4 hom., cov: 35)
  • Exomes 𝑓: 0.0015 (63 hom.)
• Consequence: CDT1 NM_030928.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.89
• Publications: 1 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=-0.69).
• BP6: Variant 16-88805775-C-T is Benign according to our data. Variant chr16-88805775-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.89 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000958 (146/152350) while in subpopulation SAS AF = 0.0292 (141/4834). AF 95% confidence interval is 0.0252. There are 4 homozygotes in GnomAd4. There are 103 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AD,AR gene

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.738C>T	p.Ser246Ser	synonymous	Exon 5 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.738C>T	p.Ser246Ser	synonymous	Exon 5 of 10	ENSP00000301019.4	Q9H211
	CDT1	ENST00000929785.1		c.738C>T	p.Ser246Ser	synonymous	Exon 5 of 10	ENSP00000599844.1
	CDT1	ENST00000569140.1	TSL:3	c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 5	ENSP00000456926.1	H3BSY1

Frequencies

GnomAD3 genomes AF: 0.000952 AC: 145 AN: 152232 Hom.: 4 Cov.: 35

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00303 AC: 757 AN: 250040 AF XY: 0.00401

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00153 AC: 2234 AN: 1460810 Hom.: 63 Cov.: 69 AF XY: 0.00219 AC XY: 1595 AN XY: 726688

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0245 AC: 2116 AN: 86256

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52424

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111956

Other (OTH) AF: 0.00166 AC: 100 AN: 60378

GnomAD4 genome AF: 0.000958 AC: 146 AN: 152350 Hom.: 4 Cov.: 35 AF XY: 0.00138 AC XY: 103 AN XY: 74494

African (AFR) AF: 0.0000240 AC: 1 AN: 41586

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0292 AC: 141 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000427 Hom.: 1

Bravo AF: 0.000227

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		-3.9
PromoterAI		-0.0061	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200892812; hg19: chr16-88872183; COSMIC: COSV56349070; COSMIC: COSV56349070;