NM_006348.5:c.1109-7404G>C

Variant names:

• chr7-107305750-C-G
• rs2299421
• NM_006348.5:c.1109-7404G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

COG5 Gene-Disease associations (from GenCC):

• COG5-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006348.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	NM_006348.5	MANE Select	c.1109-7404G>C		intron	N/A	NP_006339.4
	COG5	NM_181733.4		c.1109-7404G>C		intron	N/A	NP_859422.3
	COG5	NM_001161520.2		c.1109-7404G>C		intron	N/A	NP_001154992.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.1109-7404G>C		intron	N/A	ENSP00000297135.4
	COG5	ENST00000347053.8	TSL:1	c.1109-7404G>C		intron	N/A	ENSP00000334703.3
	COG5	ENST00000393603.7	TSL:1	c.1109-7404G>C		intron	N/A	ENSP00000377228.3

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

African (AFR) AF: 0.736 AC: 30392 AN: 41302

American (AMR) AF: 0.342 AC: 5199 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2254 AN: 5048

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4818

European-Finnish (FIN) AF: 0.305 AC: 3210 AN: 10508

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20742 AN: 67906

Other (OTH) AF: 0.389 AC: 816 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2299421; hg19: chr7-106946195;