2-147943530-GAAAAA-GAAAAAA

Position:

• chr2-147943530-GAAAAA-GAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_181741.4(ORC4):​c.763-9_763-8insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: ORC4 NM_181741.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

Genes affected

ORC4 (HGNC:8490): (origin recognition complex subunit 4) 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. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-147943530-G-GA is Benign according to our data. Variant chr2-147943530-G-GA is described in ClinVar as [Benign]. Clinvar id is 770872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000396 (52/131276) while in subpopulation SAS AF= 0.00276 (11/3980). AF 95% confidence interval is 0.00155. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC4	NM_181741.4	c.763-9_763-8insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392857.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC4	ENST00000392857.10	c.763-9_763-8insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_181741.4	P1

Frequencies

GnomAD3 genomes AF: 0.000396 AC: 52 AN: 131258 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000657

Gnomad SAS AF: 0.00275

Gnomad FIN AF: 0.000547

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000472

Gnomad OTH AF: 0.00109

GnomAD4 exome AF: 0.0126 AC: 12966 AN: 1031142 Hom.: 0 Cov.: 0 AF XY: 0.0121 AC XY: 6375 AN XY: 528188

Gnomad4 AFR exome AF: 0.00619

Gnomad4 AMR exome AF: 0.00505

Gnomad4 ASJ exome AF: 0.00788

Gnomad4 EAS exome AF: 0.00487

Gnomad4 SAS exome AF: 0.00956

Gnomad4 FIN exome AF: 0.00760

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.000396 AC: 52 AN: 131276 Hom.: 0 Cov.: 0 AF XY: 0.000410 AC XY: 26 AN XY: 63356

Gnomad4 AFR AF: 0.0000541

Gnomad4 AMR AF: 0.000151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000659

Gnomad4 SAS AF: 0.00276

Gnomad4 FIN AF: 0.000547

Gnomad4 NFE AF: 0.000472

Gnomad4 OTH AF: 0.00109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs66919703; hg19: chr2-148701099;