Variant 6-87590167-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012381.4(ORC3):c.-2C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,613,964 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 33)

Exomes 𝑓: 0.014 ( 177 hom. )

Consequence

ORC3
NM_012381.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0740

Variant links:

Genes affected

ORC3 (HGNC:8489): (origin recognition complex subunit 3) The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. Studies of a similar gene in Drosophila suggested a possible role of this protein in neuronal proliferation and olfactory memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

ORC3 links:

ORC3 (HGNC:):

ORC3 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=-0.76).

BP6

Variant 6-87590167-C-G is Benign according to our data. Variant chr6-87590167-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1186090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0116 (1767/152366) while in subpopulation NFE AF= 0.0172 (1169/68036). AF 95% confidence interval is 0.0164. There are 18 homozygotes in gnomad4. There are 917 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORC3	NM_012381.4 linkuse as main transcript	c.-2C>G		5_prime_UTR_variant	1/20	ENST00000392844.8	NP_036513.2	Q9UBD5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844 linkuse as main transcript	c.-2C>G		5_prime_UTR_variant	1/20	1	NM_012381.4	ENSP00000376586.3		Q9UBD5-1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1767

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00955

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.0114

AC:

2873

AN:

251466

Hom.:

AF XY:

0.0114

AC XY:

1546

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00604

Gnomad ASJ exome

AF:

0.00794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.0139

AC:

20321

AN:

1461598

Hom.:

177

Cov.:

AF XY:

0.0138

AC XY:

10004

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.00657

Gnomad4 ASJ exome

AF:

0.00865

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.0278

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0116

AC:

1767

AN:

152366

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

917

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00954

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00923

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0140

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.1

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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