rs2299421

chr7-107305750-C-Gchr7-107305750-C-T

Variant summary

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

The NM_006348.5(COG5):c.1109-7404G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,536 control chromosomes in the GnomAD database, including 16,924 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 0.43 (16924 hom., cov: 29)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919

Genes affected

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG5	NM_006348.5	c.1109-7404G>C		intron_variant		ENST00000297135.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG5	ENST00000297135.9	c.1109-7404G>C		intron_variant		1	NM_006348.5	P2
COG5	ENST00000347053.8	c.1109-7404G>C		intron_variant		1		A2
COG5	ENST00000393603.7	c.1109-7404G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65261 AN: 151414 Hom.: 16885 Cov.: 29

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.431 AC: 65362 AN: 151536 Hom.: 16924 Cov.: 29 AF XY: 0.427 AC XY: 31608 AN XY: 74028

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.389

Alfa AF: 0.383 Hom.: 1606

Bravo AF: 0.453

Asia WGS AF: 0.345 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.1
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: rs2299421; hg19: chr7-106946195;