NM_006348.5:c.*828C>G

Variant names:

• chr7-107202688-G-C
• rs7981
• NM_006348.5:c.*828C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006348.5(COG5):​c.*828C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,962 control chromosomes in the GnomAD database, including 2,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2329 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: COG5 NM_006348.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0510
• 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]

HBP1 (HGNC:23200): (HMG-box transcription factor 1) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of lipid transport; negative regulation of reactive oxygen species biosynthetic process; and negative regulation of transcription by RNA polymerase II. Located in nuclear speck. Biomarker of osteoarthritis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-107202688-G-C is Benign according to our data. Variant chr7-107202688-G-C is described in ClinVar as Benign. ClinVar VariationId is 358442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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.*828C>G		3_prime_UTR	Exon 22 of 22	NP_006339.4
	COG5	NM_181733.4		c.*828C>G		3_prime_UTR	Exon 21 of 21	NP_859422.3	A0AAA9X096
	COG5	NM_001379511.1		c.*828C>G		3_prime_UTR	Exon 21 of 21	NP_001366440.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.*828C>G		3_prime_UTR	Exon 22 of 22	ENSP00000297135.4	Q9UP83-4
	COG5	ENST00000347053.8	TSL:1	c.*828C>G		3_prime_UTR	Exon 21 of 21	ENSP00000334703.3	A0AAA9X096
	COG5	ENST00000889949.1		c.*828C>G		3_prime_UTR	Exon 23 of 23	ENSP00000560008.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23852 AN: 151842 Hom.: 2334 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.157 AC: 23842 AN: 151960 Hom.: 2329 Cov.: 32 AF XY: 0.155 AC XY: 11491 AN XY: 74250

African (AFR) AF: 0.0428 AC: 1775 AN: 41476

American (AMR) AF: 0.168 AC: 2566 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3466

East Asian (EAS) AF: 0.139 AC: 715 AN: 5162

South Asian (SAS) AF: 0.180 AC: 866 AN: 4816

European-Finnish (FIN) AF: 0.170 AC: 1787 AN: 10536

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14731 AN: 67940

Other (OTH) AF: 0.165 AC: 347 AN: 2108

Alfa AF: 0.0948 Hom.: 161

Bravo AF: 0.155

Asia WGS AF: 0.172 AC: 596 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	COG5-congenital disorder of glycosylation (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		-0.051
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7981; hg19: chr7-106843133;