rs150001655

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018714.3(COG1):c.529A>G(p.Ile177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000983 in 1,613,850 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I177S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0050 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 6 hom. )

Consequence

COG1
NM_018714.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.70

Publications

5 publications found

Variant links:

Genes affected

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

COG1 Gene-Disease associations (from GenCC):

COG1-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

COG1 links:

ENSG00000264860 (HGNC:):

ENSG00000264860 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=0.008609146).

BP6

Variant 17-73196720-A-G is Benign according to our data. Variant chr17-73196720-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00501 (762/152164) while in subpopulation AFR AF = 0.0169 (702/41512). AF 95% confidence interval is 0.0159. There are 6 homozygotes in GnomAd4. There are 333 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG1	NM_018714.3	MANE Select	c.529A>G	p.Ile177Val	missense	Exon 2 of 14	NP_061184.1	Q8WTW3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COG1	ENST00000299886.9	TSL:1 MANE Select	c.529A>G	p.Ile177Val	missense	Exon 2 of 14	ENSP00000299886.4	Q8WTW3
COG1	ENST00000438720.7	TSL:1	c.526A>G	p.Ile176Val	missense	Exon 2 of 13	ENSP00000400111.3	E9PBL8
COG1	ENST00000923183.1		c.523A>G	p.Ile175Val	missense	Exon 2 of 14	ENSP00000593242.1

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

759

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00137

AC:

343

AN:

250278

AF XY:

0.000953

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000710

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000564

AC:

824

AN:

1461686

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

351

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.0149

AC:

500

AN:

33476

American (AMR)

AF:

0.00157

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000809

AC:

AN:

1111910

Other (OTH)

AF:

0.00147

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00501

AC:

762

AN:

152164

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

333

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0169

AC:

702

AN:

41512

American (AMR)

AF:

0.00222

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68006

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00251

Hom.:

Bravo

AF:

0.00553

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00160

AC:

194

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

COG1 congenital disorder of glycosylation (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.9

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

1.7

PrimateAI

Benign

0.30

PROVEAN

Benign

0.35

REVEL

Benign

0.058

Sift

Benign

0.88

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.051

MVP

0.23

MPC

0.084

ClinPred

0.0028

GERP RS

0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over