Variant 22-19480194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003504.5(CDC45):c.88C>T(p.Leu30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,613,868 control chromosomes in the GnomAD database, including 1,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 292 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1377 hom. )

Consequence

CDC45
NM_003504.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00100

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 22-19480194-C-T is Benign according to our data. Variant chr22-19480194-C-T is described in ClinVar as [Benign]. Clinvar id is 1168874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.001 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 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.88C>T	p.Leu30=	synonymous_variant	2/19	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.88C>T	p.Leu30=	synonymous_variant	2/19	1	NM_003504.5	ENSP00000263201	P1	O75419-1

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7565

AN:

152094

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0840

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0776

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.0532

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0369

GnomAD3 exomes

AF:

0.0523

AC:

13147

AN:

251358

Hom.:

579

AF XY:

0.0498

AC XY:

6765

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0840

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.0848

Gnomad FIN exome

AF:

0.0494

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0352

GnomAD4 exome

AF:

0.0297

AC:

43369

AN:

1461656

Hom.:

1377

Cov.:

AF XY:

0.0307

AC XY:

22307

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0887

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.0851

Gnomad4 FIN exome

AF:

0.0425

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0357

GnomAD4 genome

AF:

0.0498

AC:

7576

AN:

152212

Hom.:

292

Cov.:

AF XY:

0.0532

AC XY:

3962

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0840

Gnomad4 AMR

AF:

0.0779

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.0963

Gnomad4 FIN

AF:

0.0532

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0365

Alfa

AF:

0.0264

Hom.:

Bravo

AF:

0.0523

Asia WGS

AF:

0.107

AC:

370

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.94

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