rs12046196

chr1-230679451-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007357.3(COG2):c.1166+399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 154,946 control chromosomes in the GnomAD database, including 1,643 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 0.12 (1621 hom., cov: 32)
  • Exomes 𝑓: 0.10 (22 hom.)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG2	NM_007357.3	c.1166+399G>A		intron_variant		ENST00000366669.9
COG2	NM_001145036.2	c.1166+399G>A		intron_variant
COG2	XM_047449445.1	c.827+399G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG2	ENST00000366669.9	c.1166+399G>A		intron_variant		1	NM_007357.3	P4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18831 AN: 151978 Hom.: 1620 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.101 AC: 287 AN: 2850 Hom.: 22 Cov.: 0 AF XY: 0.0986 AC XY: 146 AN XY: 1480

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0270

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0829

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.124 AC: 18845 AN: 152096 Hom.: 1621 Cov.: 32 AF XY: 0.128 AC XY: 9498 AN XY: 74334

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.0763

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0919 Hom.: 455

Bravo AF: 0.133

Asia WGS AF: 0.265 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.14
Dann	Benign	0.63

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: rs12046196; hg19: chr1-230815197;