rs141750466

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018714.3(COG1):c.1712G>A(p.Arg571Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,614,234 control chromosomes in the GnomAD database, including 40 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R571W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0037 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 30 hom. )

Consequence

COG1
NM_018714.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 1.77

Publications

9 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), Orphanet, G2P, PanelApp Australia, ClinGen

COG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034083128).

BP6

Variant 17-73201539-G-A is Benign according to our data. Variant chr17-73201539-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 252724.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0037 (564/152348) while in subpopulation NFE AF = 0.00517 (352/68040). AF 95% confidence interval is 0.00473. There are 10 homozygotes in GnomAd4. There are 314 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG1	NM_018714.3	MANE Select	c.1712G>A	p.Arg571Gln	missense	Exon 7 of 14	NP_061184.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG1	ENST00000299886.9	TSL:1 MANE Select	c.1712G>A	p.Arg571Gln	missense	Exon 7 of 14	ENSP00000299886.4
	COG1	ENST00000438720.7	TSL:1	c.1709G>A	p.Arg570Gln	missense	Exon 7 of 13	ENSP00000400111.3

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

564

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00517

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00379

AC:

952

AN:

251366

AF XY:

0.00364

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00280

AC:

4094

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

2161

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000581

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00429

AC:

112

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0171

AC:

916

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00259

AC:

2884

AN:

1112010

Other (OTH)

AF:

0.00242

AC:

146

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

297

593

890

1186

1483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00370

AC:

564

AN:

152348

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41572

American (AMR)

AF:

0.000523

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0169

AC:

179

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00517

AC:

352

AN:

68040

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

151

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:

0.00325

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00401

AC:

487

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00249

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

COG1 congenital disorder of glycosylation (2)

not provided (2)

COG1-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.6

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.73

PhyloP100

1.8

PrimateAI

Benign

0.19

PROVEAN

Benign

0.45

REVEL

Benign

0.11

Sift

Benign

0.50

Sift4G

Benign

0.50

Polyphen

0.0050

Vest4

0.081

MVP

0.25

MPC

0.12

ClinPred

0.0026

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.041

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over