rs9450765

Positions:

• chr6-87635330-A-G
• chr6-87635330-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012381.4(ORC3):​c.1302+369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,046 control chromosomes in the GnomAD database, including 12,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12535 hom., cov: 32)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORC3	NM_012381.4	c.1302+369A>G		intron_variant		ENST00000392844.8	NP_036513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844.8	c.1302+369A>G		intron_variant		1	NM_012381.4	ENSP00000376586.3
ORC3	ENST00000257789.4	c.1302+369A>G		intron_variant		1		ENSP00000257789.4
ORC3	ENST00000546266.5	c.873+369A>G		intron_variant		2		ENSP00000444695.1
ORC3	ENST00000681069.1	n.1335+369A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61395 AN: 151926 Hom.: 12514 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.404 AC: 61453 AN: 152046 Hom.: 12535 Cov.: 32 AF XY: 0.405 AC XY: 30095 AN XY: 74304

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.402

Alfa AF: 0.392 Hom.: 15524

Bravo AF: 0.409

Asia WGS AF: 0.454 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs9450765; hg19: chr6-88345048;