rs113455884

chr16-70483921-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015386.3(COG4):c.1759C>A(p.Gln587Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0082 in 1,613,232 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (77 hom.)
• Consequence: COG4 NM_015386.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.76

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 (MetaRNN=0.007169932).
• BP6: Variant 16-70483921-G-T is Benign according to our data. Variant chr16-70483921-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 95696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00511 (778/152318) while in subpopulation NFE AF= 0.00889 (605/68028). AF 95% confidence interval is 0.00831. There are 2 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG4	NM_015386.3	c.1759C>A	p.Gln587Lys	missense_variant	14/19	ENST00000323786.10
COG4	NM_001195139.2	c.1684C>A	p.Gln562Lys	missense_variant	13/18
COG4	NM_001365426.1	c.1333C>A	p.Gln445Lys	missense_variant	15/20
COG4	NR_158212.1	n.1718C>A		non_coding_transcript_exon_variant	14/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG4	ENST00000323786.10	c.1759C>A	p.Gln587Lys	missense_variant	14/19	1	NM_015386.3	P1

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 778 AN: 152200 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00470 AC: 1178 AN: 250730 Hom.: 7 AF XY: 0.00484 AC XY: 657 AN XY: 135758

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00314

Gnomad FIN exome AF: 0.00278

Gnomad NFE exome AF: 0.00801

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00852 AC: 12450 AN: 1460914 Hom.: 77 Cov.: 31 AF XY: 0.00840 AC XY: 6105 AN XY: 726764

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00311

Gnomad4 FIN exome AF: 0.00308

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00604

GnomAD4 genome AF: 0.00511 AC: 778 AN: 152318 Hom.: 2 Cov.: 32 AF XY: 0.00489 AC XY: 364 AN XY: 74494

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00442

Gnomad4 NFE AF: 0.00889

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00685 Hom.: 5

Bravo AF: 0.00435

TwinsUK AF: 0.0121 AC: 45

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00791 AC: 68

ExAC AF: 0.00464 AC: 563

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.00682

EpiControl AF: 0.00788

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	COG4: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 01, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 25, 2013

- -

COG4-congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	17
Dann	Benign	0.86
DEOGEN2	Benign	0.0022	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0072	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	1.3	N;.
REVEL	Benign	0.091
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Vest4		0.34
MVP		0.099
MPC		0.19
ClinPred		0.0052	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		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: rs113455884; hg19: chr16-70517824;