1-230659895-A-G

Position:

• chr1-230659895-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000366669.9(COG2):​c.234+270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,100 control chromosomes in the GnomAD database, including 19,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (19211 hom., cov: 33)
• Consequence: COG2 ENST00000366669.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.520

Genes affected

COG2 (HGNC:6546): (component of oligomeric golgi complex 2) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi complex. The encoded protein specifically interacts with the USO1 vesicle docking protein and may be necessary for normal Golgi ribbon formation and trafficking of Golgi enzymes. Mutations of this gene are associated with abnormal glycosylation within the Golgi apparatus. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-230659895-A-G is Benign according to our data. Variant chr1-230659895-A-G is described in ClinVar as [Benign]. Clinvar id is 1270031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.234+270A>G		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.234+270A>G		intron_variant			NP_001138508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.234+270A>G		intron_variant		1	NM_007357.3	ENSP00000355629	P4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74833 AN: 151982 Hom.: 19175 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.493 AC: 74920 AN: 152100 Hom.: 19211 Cov.: 33 AF XY: 0.493 AC XY: 36665 AN XY: 74350

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.499

Alfa AF: 0.442 Hom.: 15141

Bravo AF: 0.508

Asia WGS AF: 0.655 AC: 2273 AN: 3478

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

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.74

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: rs2225146; hg19: chr1-230795641;