rs371269045

Variant names:

• chr16-88808287-G-A
• rs371269045
• NM_030928.4:c.*9G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-88808287-G-A
• chr16-88808287-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_030928.4(CDT1):​c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 1,577,644 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00098 (1 hom., cov: 35)
  • Exomes 𝑓: 0.00085 (4 hom.)
• Consequence: CDT1 NM_030928.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: -0.907
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000984 (150/152372) while in subpopulation AMR AF = 0.00222 (34/15310). AF 95% confidence interval is 0.00163. There are 1 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000301019.9	NP_112190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_030928.4	ENSP00000301019.4

Frequencies

GnomAD3 genomes AF: 0.000985 AC: 150 AN: 152254 Hom.: 1 Cov.: 35

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00127 AC: 239 AN: 187972 AF XY: 0.00120

Gnomad AFR exome AF: 0.000183

Gnomad AMR exome AF: 0.00225

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000608

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.000849 AC: 1210 AN: 1425272 Hom.: 4 Cov.: 34 AF XY: 0.000876 AC XY: 618 AN XY: 705818

African (AFR) AF: 0.000885 AC: 29 AN: 32766

American (AMR) AF: 0.00236 AC: 92 AN: 39018

Ashkenazi Jewish (ASJ) AF: 0.00622 AC: 158 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 38004

South Asian (SAS) AF: 0.000511 AC: 42 AN: 82218

European-Finnish (FIN) AF: 0.0000612 AC: 3 AN: 48980

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5728

European-Non Finnish (NFE) AF: 0.000649 AC: 710 AN: 1094096

Other (OTH) AF: 0.00188 AC: 111 AN: 59080

GnomAD4 genome AF: 0.000984 AC: 150 AN: 152372 Hom.: 1 Cov.: 35 AF XY: 0.00109 AC XY: 81 AN XY: 74514

African (AFR) AF: 0.000289 AC: 12 AN: 41592

American (AMR) AF: 0.00222 AC: 34 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

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: 0.00107 AC: 73 AN: 68040

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.00129

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Jun 29, 2015

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Uncertain:1

Feb 14, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.46
DANN	Benign	0.56
PhyloP100		-0.91
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: rs371269045; hg19: chr16-88874695;