Variant 22-19480364-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003504.5(CDC45):c.111+147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 761,958 control chromosomes in the GnomAD database, including 322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.031 ( 84 hom., cov: 32)

Exomes 𝑓: 0.024 ( 238 hom. )

Consequence

CDC45
NM_003504.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-19480364-G-A is Benign according to our data. Variant chr22-19480364-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212170.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC45	NM_003504.5 linkuse as main transcript	c.111+147G>A		intron_variant		ENST00000263201.7	NP_003495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC45	ENST00000263201.7 linkuse as main transcript	c.111+147G>A		intron_variant		1	NM_003504.5	ENSP00000263201	P1	O75419-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4662

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0479

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0273

GnomAD4 exome

AF:

0.0241

AC:

14712

AN:

609674

Hom.:

238

AF XY:

0.0244

AC XY:

7943

AN XY:

325176

show subpopulations

Gnomad4 AFR exome

AF:

0.0534

Gnomad4 AMR exome

AF:

0.0159

Gnomad4 ASJ exome

AF:

0.0374

Gnomad4 EAS exome

AF:

0.00187

Gnomad4 SAS exome

AF:

0.0251

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0254

Gnomad4 OTH exome

AF:

0.0277

GnomAD4 genome

AF:

0.0307

AC:

4668

AN:

152284

Hom.:

Cov.:

AF XY:

0.0297

AC XY:

2209

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0479

Gnomad4 AMR

AF:

0.0234

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0299

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.1

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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