chr7-107202688-G-C

Position:

• chr7-107202688-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG5	NM_006348.5	c.*828C>G		3_prime_UTR_variant	22/22	ENST00000297135.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG5	ENST00000297135.9	c.*828C>G		3_prime_UTR_variant	22/22	1	NM_006348.5	P2
COG5	ENST00000347053.8	c.*828C>G		3_prime_UTR_variant	21/21	1		A2

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

Gnomad4 FIN exome AF: 0.500

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

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.165

Alfa AF: 0.0948 Hom.: 161

Bravo AF: 0.155

Asia WGS AF: 0.172 AC: 596 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

COG5-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7981; hg19: chr7-106843133;