7-107293730-T-C

Variant names:

• chr7-107293730-T-C
• rs7785892
• NM_006348.5:c.1313+4412A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006348.5(COG5):​c.1313+4412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,008 control chromosomes in the GnomAD database, including 1,532 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 0.13 (1532 hom., cov: 31)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 10 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Laboratory for Molecular Medicine, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	NM_006348.5	MANE Select	c.1313+4412A>G		intron	N/A	NP_006339.4
	COG5	NM_181733.4		c.1313+4412A>G		intron	N/A	NP_859422.3
	COG5	NM_001161520.2		c.1313+4412A>G		intron	N/A	NP_001154992.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.1313+4412A>G		intron	N/A	ENSP00000297135.4
	COG5	ENST00000347053.8	TSL:1	c.1313+4412A>G		intron	N/A	ENSP00000334703.3
	COG5	ENST00000393603.7	TSL:1	c.1313+4412A>G		intron	N/A	ENSP00000377228.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19004 AN: 151890 Hom.: 1526 Cov.: 31

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.125 AC: 19019 AN: 152008 Hom.: 1532 Cov.: 31 AF XY: 0.129 AC XY: 9569 AN XY: 74296

African (AFR) AF: 0.0318 AC: 1319 AN: 41502

American (AMR) AF: 0.173 AC: 2635 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3464

East Asian (EAS) AF: 0.310 AC: 1595 AN: 5148

South Asian (SAS) AF: 0.125 AC: 601 AN: 4818

European-Finnish (FIN) AF: 0.172 AC: 1816 AN: 10558

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9916 AN: 67958

Other (OTH) AF: 0.131 AC: 277 AN: 2110

Alfa AF: 0.137 Hom.: 1424

Bravo AF: 0.127

Asia WGS AF: 0.210 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.25
PhyloP100		0.27
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: rs7785892; hg19: chr7-106934175;