chr1-230677568-A-T

Position:

• chr1-230677568-A-T

Variant summary

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

The NM_007357.3(COG2):​c.1027-1345A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,274 control chromosomes in the GnomAD database, including 1,500 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 (1500 hom., cov: 32)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.1027-1345A>T		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.1027-1345A>T		intron_variant			NP_001138508.1
COG2	XM_047449445.1	c.688-1345A>T		intron_variant			XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.1027-1345A>T		intron_variant		1	NM_007357.3	ENSP00000355629	P4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18072 AN: 152156 Hom.: 1501 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.119 AC: 18074 AN: 152274 Hom.: 1500 Cov.: 32 AF XY: 0.124 AC XY: 9242 AN XY: 74458

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.125

Alfa AF: 0.136 Hom.: 232

Bravo AF: 0.113

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.67

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: rs10495298; hg19: chr1-230813314;