NM_006348.5:c.2376-3417A>C

Variant names:

• chr7-107207047-T-G
• rs2237659
• NM_006348.5:c.2376-3417A>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.2376-3417A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,190 control chromosomes in the GnomAD database, including 3,251 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 0.19 (3251 hom., cov: 33)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783
• Publications: 13 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

LOC124901720 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG5	NM_006348.5	c.2376-3417A>C		intron_variant	Intron 21 of 21	ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.2376-3417A>C		intron_variant	Intron 21 of 21	1	NM_006348.5	ENSP00000297135.4
COG5	ENST00000347053.8	c.2313-3417A>C		intron_variant	Intron 20 of 20	1		ENSP00000334703.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29092 AN: 152072 Hom.: 3245 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.191 AC: 29104 AN: 152190 Hom.: 3251 Cov.: 33 AF XY: 0.192 AC XY: 14286 AN XY: 74402

African (AFR) AF: 0.0691 AC: 2871 AN: 41544

American (AMR) AF: 0.235 AC: 3589 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1626 AN: 5178

South Asian (SAS) AF: 0.140 AC: 676 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2441 AN: 10572

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16210 AN: 67998

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.216 Hom.: 2215

Bravo AF: 0.192

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.5
DANN	Benign	0.81
PhyloP100		0.78
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: rs2237659; hg19: chr7-106847492;