rs194846

Variant names:

• chr7-104132282-C-T
• rs194846
• NM_002553.4:c.1262+4499G>A

Variant summary

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

The NM_002553.4(ORC5):​c.1262+4499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,944 control chromosomes in the GnomAD database, including 24,302 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 0.55 (24302 hom., cov: 32)
• Consequence: ORC5 NM_002553.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 2 publications found

Genes affected

ORC5 (HGNC:8491): (origin recognition complex subunit 5) The origin recognition complex (ORC) is a highly conserved six subunit 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. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Oct 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC5	NM_002553.4	c.1262+4499G>A		intron_variant	Intron 13 of 13	ENST00000297431.9	NP_002544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC5	ENST00000297431.9	c.1262+4499G>A		intron_variant	Intron 13 of 13	1	NM_002553.4	ENSP00000297431.4
ORC5	ENST00000422497.5	n.*1195+4499G>A		intron_variant	Intron 14 of 14	2		ENSP00000393208.1
ORC5	ENST00000477223.1	n.724+4499G>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83084 AN: 151826 Hom.: 24259 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.547 AC: 83180 AN: 151944 Hom.: 24302 Cov.: 32 AF XY: 0.554 AC XY: 41121 AN XY: 74268

African (AFR) AF: 0.731 AC: 30277 AN: 41398

American (AMR) AF: 0.596 AC: 9112 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3468

East Asian (EAS) AF: 0.751 AC: 3885 AN: 5172

South Asian (SAS) AF: 0.533 AC: 2568 AN: 4814

European-Finnish (FIN) AF: 0.503 AC: 5310 AN: 10552

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28821 AN: 67938

Other (OTH) AF: 0.538 AC: 1139 AN: 2116

Alfa AF: 0.496 Hom.: 8691

Bravo AF: 0.564

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.068
DANN	Benign	0.38
PhyloP100		-0.055
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: rs194846; hg19: chr7-103772729;