rs3218723

Variant names:

• chr16-88808284-G-C
• rs3218723
• NM_030928.4:c.*6G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88808284-G-C
• chr16-88808284-G-A

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.*6G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,579,418 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 35)
  • Exomes 𝑓: 0.0022 (60 hom.)
• Consequence: CDT1 NM_030928.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.423
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-88808284-G-C is Benign according to our data. Variant chr16-88808284-G-C is described in ClinVar as Benign. ClinVar VariationId is 128663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 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.*6G>C		3_prime_UTR	Exon 10 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.*6G>C		3_prime_UTR	Exon 10 of 10	ENSP00000301019.4	Q9H211
	CDT1	ENST00000929785.1		c.*6G>C		3_prime_UTR	Exon 10 of 10	ENSP00000599844.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2403 AN: 152240 Hom.: 57 Cov.: 35

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00535 AC: 1018 AN: 190250 AF XY: 0.00498

Gnomad AFR exome AF: 0.0575

Gnomad AMR exome AF: 0.00262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00222 AC: 3165 AN: 1427060 Hom.: 60 Cov.: 34 AF XY: 0.00223 AC XY: 1577 AN XY: 706868

African (AFR) AF: 0.0546 AC: 1790 AN: 32802

American (AMR) AF: 0.00356 AC: 140 AN: 39312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25414

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38108

South Asian (SAS) AF: 0.0101 AC: 828 AN: 82382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49228

Middle Eastern (MID) AF: 0.00400 AC: 23 AN: 5744

European-Non Finnish (NFE) AF: 0.0000667 AC: 73 AN: 1094950

Other (OTH) AF: 0.00524 AC: 310 AN: 59120

GnomAD4 genome AF: 0.0159 AC: 2420 AN: 152358 Hom.: 59 Cov.: 35 AF XY: 0.0159 AC XY: 1184 AN XY: 74516

African (AFR) AF: 0.0537 AC: 2232 AN: 41584

American (AMR) AF: 0.00718 AC: 110 AN: 15312

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68034

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00175 Hom.: 2

Bravo AF: 0.0186

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.81
CADD	Benign	0.41
DANN	Benign	0.50
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

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: rs3218723; hg19: chr16-88874692;