chr16-23388733-T-C

Position:

• chr16-23388733-T-C

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.*187A>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 0.228 in 1,001,030 control chromosomes in the GnomAD database, including 30,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8718 hom., cov: 29)
  • Exomes 𝑓: 0.21 (21893 hom.)
• Consequence: COG7 NM_153603.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.907

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=-0.79).
• BP6: Variant 16-23388733-T-C is Benign according to our data. Variant chr16-23388733-T-C is described in ClinVar as [Benign]. Clinvar id is 318458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG7	NM_153603.4	c.*187A>G		3_prime_UTR_variant	17/17	ENST00000307149.10
COG7	XM_017023870.2	c.*187A>G		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG7	ENST00000307149.10	c.*187A>G		3_prime_UTR_variant	17/17	1	NM_153603.4	P1
COG7	ENST00000566364.1	n.847A>G		non_coding_transcript_exon_variant	3/3	2
COG7	ENST00000561854.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46867 AN: 151420 Hom.: 8677 Cov.: 29

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.214 AC: 181375 AN: 849492 Hom.: 21893 Cov.: 11 AF XY: 0.216 AC XY: 91563 AN XY: 422934

Gnomad4 AFR exome AF: 0.537

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.310 AC: 46974 AN: 151538 Hom.: 8718 Cov.: 29 AF XY: 0.311 AC XY: 23036 AN XY: 74028

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.286

Alfa AF: 0.256 Hom.: 717

Bravo AF: 0.318

Asia WGS AF: 0.332 AC: 1153 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 12, 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	-0.79
CADD	Benign	1.8
DANN	Benign	0.39

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: rs250588; hg19: chr16-23400054;