chr6-87651299-G-A

Variant names:

• chr6-87651299-G-A
• rs7772351
• NM_012381.4:c.1383-1817G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012381.4(ORC3):​c.1383-1817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 455,966 control chromosomes in the GnomAD database, including 39,612 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 (12351 hom., cov: 32)
  • Exomes 𝑓: 0.42 (27261 hom.)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012381.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC3	NM_012381.4	MANE Select	c.1383-1817G>A		intron	N/A	NP_036513.2
	ORC3	NM_181837.3		c.1383-1817G>A		intron	N/A	NP_862820.1
	ORC3	NM_001197259.2		c.954-1817G>A		intron	N/A	NP_001184188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC3	ENST00000392844.8	TSL:1 MANE Select	c.1383-1817G>A		intron	N/A	ENSP00000376586.3
	ORC3	ENST00000257789.4	TSL:1	c.1383-1817G>A		intron	N/A	ENSP00000257789.4
	ORC3	ENST00000508875.1	TSL:2	c.-95G>A		5_prime_UTR	Exon 1 of 2	ENSP00000475988.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60946 AN: 151896 Hom.: 12331 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.397

GnomAD2 exomes AF: 0.432 AC: 55426 AN: 128352 AF XY: 0.428

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.386

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.418 AC: 127192 AN: 303952 Hom.: 27261 Cov.: 0 AF XY: 0.418 AC XY: 72403 AN XY: 173068

African (AFR) AF: 0.387 AC: 3341 AN: 8628

American (AMR) AF: 0.546 AC: 14900 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 4119 AN: 10790

East Asian (EAS) AF: 0.384 AC: 3535 AN: 9210

South Asian (SAS) AF: 0.446 AC: 26645 AN: 59742

European-Finnish (FIN) AF: 0.424 AC: 5245 AN: 12364

Middle Eastern (MID) AF: 0.370 AC: 1030 AN: 2782

European-Non Finnish (NFE) AF: 0.393 AC: 62455 AN: 158920

Other (OTH) AF: 0.416 AC: 5922 AN: 14234

GnomAD4 genome AF: 0.401 AC: 60998 AN: 152014 Hom.: 12351 Cov.: 32 AF XY: 0.402 AC XY: 29884 AN XY: 74274

African (AFR) AF: 0.385 AC: 15978 AN: 41462

American (AMR) AF: 0.482 AC: 7363 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3466

East Asian (EAS) AF: 0.394 AC: 2031 AN: 5158

South Asian (SAS) AF: 0.447 AC: 2154 AN: 4820

European-Finnish (FIN) AF: 0.405 AC: 4276 AN: 10546

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26635 AN: 67966

Other (OTH) AF: 0.401 AC: 847 AN: 2114

Alfa AF: 0.396 Hom.: 10115

Bravo AF: 0.405

Asia WGS AF: 0.453 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.081
DANN	Benign	0.51
PhyloP100		-2.3
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7772351; hg19: chr6-88361017;