rs13447284

Variant names:

• chr22-19518008-C-T
• rs13447284
• NM_003504.5:c.1637-836C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003504.5(CDC45):​c.1637-836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,310 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (222 hom., cov: 33)
• Consequence: CDC45 NM_003504.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 2 publications found

Genes affected

CDC45 (HGNC:1739): (cell division cycle 45) The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes. This protein has been shown to interact with MCM7 and DNA polymerase alpha. Studies of the similar gene in Xenopus suggested that this protein play a pivotal role in the loading of DNA polymerase alpha onto chromatin. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

CDC45 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Meier-Gorlin syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287652 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC45	NM_003504.5	c.1637-836C>T		intron_variant	Intron 17 of 18	ENST00000263201.7	NP_003495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC45	ENST00000263201.7	c.1637-836C>T		intron_variant	Intron 17 of 18	1	NM_003504.5	ENSP00000263201.2

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7052 AN: 152192 Hom.: 222 Cov.: 33

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.0642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0464 AC: 7062 AN: 152310 Hom.: 222 Cov.: 33 AF XY: 0.0463 AC XY: 3452 AN XY: 74478

African (AFR) AF: 0.0190 AC: 791 AN: 41574

American (AMR) AF: 0.0767 AC: 1173 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3472

East Asian (EAS) AF: 0.0415 AC: 215 AN: 5178

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4830

European-Finnish (FIN) AF: 0.0398 AC: 423 AN: 10622

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0579 AC: 3940 AN: 68018

Other (OTH) AF: 0.0640 AC: 135 AN: 2110

Alfa AF: 0.0551 Hom.: 211

Bravo AF: 0.0491

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.64
PhyloP100		-0.92
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: rs13447284; hg19: chr22-19505531;