rs6930600

Positions:

• chr6-87640069-G-A

Variant summary

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

The NM_012381.4(ORC3):​c.1382+3583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,870 control chromosomes in the GnomAD database, including 27,891 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 0.60 (27891 hom., cov: 31)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC3	NM_012381.4	c.1382+3583G>A		intron_variant		ENST00000392844.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC3	ENST00000392844.8	c.1382+3583G>A		intron_variant		1	NM_012381.4	A1
ORC3	ENST00000257789.4	c.1382+3583G>A		intron_variant		1		P4
ORC3	ENST00000546266.5	c.953+3583G>A		intron_variant		2
ORC3	ENST00000681069.1	n.1415+3583G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90908 AN: 151752 Hom.: 27844 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.599 AC: 91020 AN: 151870 Hom.: 27891 Cov.: 31 AF XY: 0.598 AC XY: 44424 AN XY: 74228

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.591

Alfa AF: 0.551 Hom.: 10604

Bravo AF: 0.619

Asia WGS AF: 0.635 AC: 2211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.0
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs6930600; hg19: chr6-88349787;