chr16-23388873-G-A

Position:

• chr16-23388873-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153603.4(COG7):​c.*47C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,611,738 control chromosomes in the GnomAD database, including 28,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3586 hom., cov: 29)
  • Exomes 𝑓: 0.18 (25399 hom.)
• Consequence: COG7 NM_153603.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.589

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-23388873-G-A is Benign according to our data. Variant chr16-23388873-G-A is described in ClinVar as [Benign]. Clinvar id is 318459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG7	NM_153603.4	c.*47C>T		3_prime_UTR_variant	17/17	ENST00000307149.10
COG7	XM_017023870.2	c.*47C>T		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG7	ENST00000307149.10	c.*47C>T		3_prime_UTR_variant	17/17	1	NM_153603.4	P1
COG7	ENST00000566364.1	n.707C>T		non_coding_transcript_exon_variant	3/3	2
COG7	ENST00000561854.1	c.*452C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 31923 AN: 150880 Hom.: 3578 Cov.: 29

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.192

GnomAD3 exomes AF: 0.200 AC: 50177 AN: 250604 Hom.: 5377 AF XY: 0.201 AC XY: 27222 AN XY: 135472

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.182 AC: 265771 AN: 1460736 Hom.: 25399 Cov.: 32 AF XY: 0.184 AC XY: 133495 AN XY: 726648

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.212 AC: 31965 AN: 151002 Hom.: 3586 Cov.: 29 AF XY: 0.215 AC XY: 15817 AN XY: 73688

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.197

Alfa AF: 0.178 Hom.: 2585

Bravo AF: 0.207

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

COG7 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.54

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: rs250587; hg19: chr16-23400194;