7-104171393-G-A

Variant names:

• chr7-104171393-G-A
• rs3808008
• NM_002553.4:c.825-2868C>T

Variant summary

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

The NM_002553.4(ORC5):​c.825-2868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,996 control chromosomes in the GnomAD database, including 16,276 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 0.43 (16276 hom., cov: 32)
• Consequence: ORC5 NM_002553.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC5	NM_002553.4	c.825-2868C>T		intron_variant	Intron 8 of 13	ENST00000297431.9	NP_002544.1
ORC5	NM_181747.4	c.825-2868C>T		intron_variant	Intron 8 of 8		NP_859531.1
ORC5	XM_047420431.1	c.685-2868C>T		intron_variant	Intron 6 of 7		XP_047276387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC5	ENST00000297431.9	c.825-2868C>T		intron_variant	Intron 8 of 13	1	NM_002553.4	ENSP00000297431.4
ORC5	ENST00000447452.6	c.825-2868C>T		intron_variant	Intron 8 of 8	1		ENSP00000395747.2
ORC5	ENST00000422497.5	n.*758-2868C>T		intron_variant	Intron 9 of 14	2		ENSP00000393208.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65204 AN: 151878 Hom.: 16268 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.429 AC: 65222 AN: 151996 Hom.: 16276 Cov.: 32 AF XY: 0.424 AC XY: 31488 AN XY: 74266

African (AFR) AF: 0.186 AC: 7722 AN: 41480

American (AMR) AF: 0.394 AC: 6023 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1810 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1303 AN: 5170

South Asian (SAS) AF: 0.467 AC: 2251 AN: 4818

European-Finnish (FIN) AF: 0.498 AC: 5239 AN: 10524

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39132 AN: 67954

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.525 Hom.: 41301

Bravo AF: 0.408

Asia WGS AF: 0.365 AC: 1268 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.51
PhyloP100		-0.53
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: rs3808008; hg19: chr7-103811841;