chr16-70510030-G-C

Position:

• chr16-70510030-G-C

Variant summary

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

The NM_015386.3(COG4):​c.739-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,609,788 control chromosomes in the GnomAD database, including 6,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (3652 hom., cov: 32)
  • Exomes 𝑓: 0.013 (3189 hom.)
• Consequence: COG4 NM_015386.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002747
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.393

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-70510030-G-C is Benign according to our data. Variant chr16-70510030-G-C is described in ClinVar as [Benign]. Clinvar id is 320377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG4	NM_015386.3	c.739-9C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000323786.10
COG4	NM_001195139.2	c.727-9C>G		splice_polypyrimidine_tract_variant, intron_variant
COG4	NM_001365426.1	c.313-9C>G		splice_polypyrimidine_tract_variant, intron_variant
COG4	NR_158212.1	n.750-9C>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG4	ENST00000323786.10	c.739-9C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015386.3	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18253 AN: 152042 Hom.: 3648 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.0798

GnomAD3 exomes AF: 0.0326 AC: 8169 AN: 250946 Hom.: 1434 AF XY: 0.0242 AC XY: 3278 AN XY: 135722

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.0210

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.0189

GnomAD4 exome AF: 0.0133 AC: 19356 AN: 1457628 Hom.: 3189 Cov.: 29 AF XY: 0.0117 AC XY: 8458 AN XY: 725438

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000778

Gnomad4 FIN exome AF: 0.0000938

Gnomad4 NFE exome AF: 0.00134

Gnomad4 OTH exome AF: 0.0290

GnomAD4 genome AF: 0.120 AC: 18287 AN: 152160 Hom.: 3652 Cov.: 32 AF XY: 0.117 AC XY: 8695 AN XY: 74402

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00266

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0116 Hom.: 48

Bravo AF: 0.135

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

COG4-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

COG4-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.6
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.062
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: rs16970243; hg19: chr16-70543933;