1-230660494-C-T

Position:

• chr1-230660494-C-T

Variant summary

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

The NM_007357.3(COG2):​c.235-264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,134 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 0.060 (565 hom., cov: 33)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

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=-0.72).
• BP6: Variant 1-230660494-C-T is Benign according to our data. Variant chr1-230660494-C-T is described in ClinVar as [Benign]. Clinvar id is 1248042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.235-264C>T		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.235-264C>T		intron_variant			NP_001138508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.235-264C>T		intron_variant		1	NM_007357.3	ENSP00000355629	P4

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9039 AN: 152016 Hom.: 565 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.0943

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0596 AC: 9061 AN: 152134 Hom.: 565 Cov.: 33 AF XY: 0.0603 AC XY: 4487 AN XY: 74382

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.00520

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0384 Hom.: 40

Bravo AF: 0.0656

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

Apr 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.9
DANN	Benign	0.64

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: rs78361742; hg19: chr1-230796240;