rs3931036

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T162V) has been classified as Uncertain significance.

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

Publications

47 publications found

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 Gene-Disease associations (from GenCC):

COG4-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, PanelApp Australia, Ambry Genetics
microcephalic osteodysplastic dysplasia, Saul-Wilson type
Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

COG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 95697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG4	NM_015386.3 link	c.485C>T	p.Thr162Ile	missense_variant	Exon 4 of 19	ENST00000323786.10	NP_056201.2	Q9H9E3J3KNI1Q8N8L9
COG4	NM_001195139.2 link	c.473C>T	p.Thr158Ile	missense_variant	Exon 4 of 18		NP_001182068.2	Q9H9E3A0A0A0MS45Q8N8L9
COG4	NM_001365426.1 link	c.59C>T	p.Thr20Ile	missense_variant	Exon 5 of 20		NP_001352355.1
COG4	NR_158212.1 link	n.496C>T		non_coding_transcript_exon_variant	Exon 4 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10 link	c.485C>T	p.Thr162Ile	missense_variant	Exon 4 of 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

GnomAD2 exomes

AF:

0.945

AC:

237617

AN:

251324

AF XY:

0.947

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 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

African (AFR)

AF:

0.991

AC:

33163

AN:

33480

American (AMR)

AF:

0.899

AC:

40186

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.955

AC:

24955

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39695

AN:

39700

South Asian (SAS)

AF:

0.957

AC:

82563

AN:

86252

European-Finnish (FIN)

AF:

0.947

AC:

50594

AN:

53414

Middle Eastern (MID)

AF:

0.981

AC:

5658

AN:

5766

European-Non Finnish (NFE)

AF:

0.935

AC:

1039251

AN:

1111928

Other (OTH)

AF:

0.949

AC:

57292

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

4511

9023

13534

18046

22557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21566

43132

64698

86264

107830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.954

AC:

145224

AN:

152204

Hom.:

69365

Cov.:

AF XY:

0.955

AC XY:

71078

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.989

AC:

41099

AN:

41536

American (AMR)

AF:

0.923

AC:

14095

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

3287

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5172

AN:

5178

South Asian (SAS)

AF:

0.964

AC:

4643

AN:

4818

European-Finnish (FIN)

AF:

0.943

AC:

9993

AN:

10592

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.937

AC:

63763

AN:

68018

Other (OTH)

AF:

0.964

AC:

2033

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.945

Hom.:

224530

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

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

May 28, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

COG4-congenital disorder of glycosylation

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microcephalic osteodysplastic dysplasia, Saul-Wilson type

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

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

PhyloP100

7.0

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over