Variant 22-19479939-G-T 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.-30G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 1,611,828 control chromosomes in the GnomAD database, including 2,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 227 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2522 hom. )

Consequence

CDC45
NM_003504.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-19479939-G-T is Benign according to our data. Variant chr22-19479939-G-T is described in ClinVar as [Benign]. Clinvar id is 1252951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0745 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.-30G>T		5_prime_UTR_variant	1/19	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.-30G>T		5_prime_UTR_variant	1/19	1	NM_003504.5	ENSP00000263201	P1	O75419-1

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

7345

AN:

152180

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0779

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.0414

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0641

GnomAD3 exomes

AF:

0.0562

AC:

13891

AN:

247054

Hom.:

484

AF XY:

0.0543

AC XY:

7327

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0583

Gnomad EAS exome

AF:

0.0436

Gnomad SAS exome

AF:

0.0351

Gnomad FIN exome

AF:

0.0404

Gnomad NFE exome

AF:

0.0571

Gnomad OTH exome

AF:

0.0628

GnomAD4 exome

AF:

0.0561

AC:

81933

AN:

1459530

Hom.:

2522

Cov.:

AF XY:

0.0557

AC XY:

40435

AN XY:

726094

show subpopulations

Gnomad4 AFR exome

AF:

0.0240

Gnomad4 AMR exome

AF:

0.0950

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.0562

Gnomad4 SAS exome

AF:

0.0355

Gnomad4 FIN exome

AF:

0.0403

Gnomad4 NFE exome

AF:

0.0578

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0483

AC:

7362

AN:

152298

Hom.:

227

Cov.:

AF XY:

0.0482

AC XY:

3591

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.0782

Gnomad4 ASJ

AF:

0.0588

Gnomad4 EAS

AF:

0.0415

Gnomad4 SAS

AF:

0.0305

Gnomad4 FIN

AF:

0.0402

Gnomad4 NFE

AF:

0.0581

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0555

Hom.:

Bravo

AF:

0.0511

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

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	clinical testing	GeneDx	Oct 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.7

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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