rs34343511

Positions:

chr16-46697501-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014321.4(ORC6):c.675T>C(p.Asp225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,613,482 control chromosomes in the GnomAD database, including 565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 45 hom., cov: 33)

Exomes 𝑓: 0.024 ( 520 hom. )

Consequence

ORC6
NM_014321.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0550

Variant links:

Genes affected

ORC6 (HGNC:17151): (origin recognition complex subunit 6) 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. Gene silencing studies with small interfering RNA demonstrated that this protein plays an essential role in coordinating chromosome replication and segregation with cytokinesis. [provided by RefSeq, Oct 2010]

ORC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-46697501-T-C is Benign according to our data. Variant chr16-46697501-T-C is described in ClinVar as [Benign]. Clinvar id is 129866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-46697501-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.055 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2831/152268) while in subpopulation NFE AF= 0.0258 (1752/68018). AF 95% confidence interval is 0.0248. There are 45 homozygotes in gnomad4. There are 1396 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC6	NM_014321.4 linkuse as main transcript	c.675T>C	p.Asp225=	synonymous_variant	7/7	ENST00000219097.7
ORC6	NR_037620.2 linkuse as main transcript	n.781T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC6	ENST00000219097.7 linkuse as main transcript	c.675T>C	p.Asp225=	synonymous_variant	7/7	1	NM_014321.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2833

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00471

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0390

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0186

AC:

4683

AN:

251270

Hom.:

AF XY:

0.0190

AC XY:

2583

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00454

Gnomad FIN exome

AF:

0.0363

Gnomad NFE exome

AF:

0.0259

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0241

AC:

35171

AN:

1461214

Hom.:

520

Cov.:

AF XY:

0.0238

AC XY:

17291

AN XY:

726926

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00468

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0213

GnomAD4 genome

AF:

0.0186

AC:

2831

AN:

152268

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1396

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00470

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0390

Gnomad4 NFE

AF:

0.0258

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0254

EpiControl

AF:

0.0244

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 17, 2013

- -

Meier-Gorlin syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.0

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over