rs3931036

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015386.3(COG4):c.485C>T(p.Thr162Ile) variant causes a missense change. The variant allele was found at a frequency of 0.941 in 1,613,988 control chromosomes in the GnomAD database, including 714,932 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69365 hom., cov: 30)

Exomes 𝑓: 0.94 ( 645567 hom. )

Consequence

COG4
NM_015386.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 7.02

Variant links:

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]

COG4 links:

COG4 (HGNC:):

COG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.8243927E-7).

BP6

Variant 16-70514394-G-A is Benign according to our data. Variant chr16-70514394-G-A is described in ClinVar as [Benign]. Clinvar id is 95697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-70514394-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG4	NM_015386.3 linkuse as main transcript	c.485C>T	p.Thr162Ile	missense_variant	4/19	ENST00000323786.10	NP_056201.2	Q9H9E3J3KNI1Q8N8L9
COG4	NM_001195139.2 linkuse as main transcript	c.473C>T	p.Thr158Ile	missense_variant	4/18		NP_001182068.2	Q9H9E3A0A0A0MS45Q8N8L9
COG4	NM_001365426.1 linkuse as main transcript	c.59C>T	p.Thr20Ile	missense_variant	5/20		NP_001352355.1
COG4	NR_158212.1 linkuse as main transcript	n.496C>T		non_coding_transcript_exon_variant	4/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10 linkuse as main transcript	c.485C>T	p.Thr162Ile	missense_variant	4/19	1	NM_015386.3	ENSP00000315775.5		J3KNI1

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145106

AN:

152086

Hom.:

69305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.989

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.923

Gnomad ASJ

AF:

0.947

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.964

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.937

Gnomad OTH

AF:

0.963

GnomAD3 exomes

AF:

0.945

AC:

237617

AN:

251324

Hom.:

112444

AF XY:

0.947

AC XY:

128581

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.991

Gnomad AMR exome

AF:

0.899

Gnomad ASJ exome

AF:

0.955

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.958

Gnomad FIN exome

AF:

0.945

Gnomad NFE exome

AF:

0.939

Gnomad OTH exome

AF:

0.955

GnomAD4 exome

AF:

0.940

AC:

1373357

AN:

1461784

Hom.:

645567

Cov.:

AF XY:

0.940

AC XY:

683429

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.991

Gnomad4 AMR exome

AF:

0.899

Gnomad4 ASJ exome

AF:

0.955

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.957

Gnomad4 FIN exome

AF:

0.947

Gnomad4 NFE exome

AF:

0.935

Gnomad4 OTH exome

AF:

0.949

GnomAD4 genome

AF:

0.954

AC:

145224

AN:

152204

Hom.:

69365

Cov.:

AF XY:

0.955

AC XY:

71078

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.989

Gnomad4 AMR

AF:

0.923

Gnomad4 ASJ

AF:

0.947

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.964

Gnomad4 FIN

AF:

0.943

Gnomad4 NFE

AF:

0.937

Gnomad4 OTH

AF:

0.964

Alfa

AF:

0.945

Hom.:

165139

Bravo

AF:

0.954

TwinsUK

AF:

0.924

AC:

3428

ALSPAC

AF:

0.928

AC:

3575

ESP6500AA

AF:

0.987

AC:

4339

ESP6500EA

AF:

0.940

AC:

8080

ExAC

AF:

0.947

AC:

115010

Asia WGS

AF:

0.980

AC:

3409

AN:

3478

EpiCase

AF:

0.942

EpiControl

AF:

0.947

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 28, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

COG4-congenital disorder of glycosylation

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Microcephalic osteodysplastic dysplasia, Saul-Wilson type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.0040

T;T;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.44

T;T;T;T

MetaRNN

Benign

5.8e-7

T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

3.7

N;.;N;.

REVEL

Benign

0.26

Sift

Benign

1.0

T;.;T;.

Sift4G

Benign

1.0

T;T;T;.

Vest4

0.22

MPC

0.16

ClinPred

0.0099

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over