Variant 22-19480129-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003504.5(CDC45):c.52-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,613,198 control chromosomes in the GnomAD database, including 265,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19666 hom., cov: 32)

Exomes 𝑓: 0.58 ( 246126 hom. )

Consequence

CDC45
NM_003504.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.411

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 22-19480129-T-C is Benign according to our data. Variant chr22-19480129-T-C is described in ClinVar as [Benign]. Clinvar id is 1234967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC45	NM_003504.5 link	c.52-29T>C		intron_variant		ENST00000263201.7	NP_003495.1	O75419-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC45	ENST00000263201.7 link	c.52-29T>C		intron_variant		1	NM_003504.5	ENSP00000263201.2		O75419-1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73098

AN:

151968

Hom.:

19650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.633

Gnomad FIN

AF:

0.517

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.532

GnomAD3 exomes

AF:

0.552

AC:

138530

AN:

251146

Hom.:

39769

AF XY:

0.566

AC XY:

76854

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.540

Gnomad ASJ exome

AF:

0.671

Gnomad EAS exome

AF:

0.427

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.589

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.576

AC:

840944

AN:

1461112

Hom.:

246126

Cov.:

AF XY:

0.579

AC XY:

421056

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.539

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.650

Gnomad4 FIN exome

AF:

0.526

Gnomad4 NFE exome

AF:

0.588

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.481

AC:

73148

AN:

152086

Hom.:

19666

Cov.:

AF XY:

0.482

AC XY:

35806

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.553

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.634

Gnomad4 FIN

AF:

0.517

Gnomad4 NFE

AF:

0.593

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.551

Hom.:

7884

Bravo

AF:

0.468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.9

DANN

Benign

0.62

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over