rs147588256

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_018714.3(COG1):c.2900C>G(p.Pro967Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000502 in 1,614,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

COG1
NM_018714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 4.18

Publications

2 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 links:

VCF1 (HGNC:25918): (VCP nuclear cofactor family member 1)

VCF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.082861245).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000322 (49/152352) while in subpopulation NFE AF = 0.000544 (37/68020). AF 95% confidence interval is 0.000405. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COG1	NM_018714.3	MANE Select	c.2900C>G	p.Pro967Arg	missense	Exon 14 of 14	NP_061184.1	Q8WTW3
VCF1	NM_001098832.2	MANE Select	c.*1121G>C		3_prime_UTR	Exon 4 of 4	NP_001092302.1	Q969W3-2
VCF1	NM_032837.3		c.*1121G>C		3_prime_UTR	Exon 3 of 3	NP_116226.2	Q969W3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COG1	ENST00000299886.9	TSL:1 MANE Select	c.2900C>G	p.Pro967Arg	missense	Exon 14 of 14	ENSP00000299886.4	Q8WTW3
VCF1	ENST00000405159.8	TSL:1 MANE Select	c.*1121G>C		3_prime_UTR	Exon 4 of 4	ENSP00000384832.3	Q969W3-2
COG1	ENST00000438720.7	TSL:1	c.*1068C>G		3_prime_UTR	Exon 13 of 13	ENSP00000400111.3	E9PBL8

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000490

AC:

123

AN:

251270

AF XY:

0.000501

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000925

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000521

AC:

761

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000496

AC XY:

361

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000622

AC:

692

AN:

1112008

Other (OTH)

AF:

0.000563

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000322

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000663

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

COG1 congenital disorder of glycosylation (3)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Benign

0.13

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0049

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

4.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Uncertain

0.021

Sift4G

Uncertain

0.046

Polyphen

0.73

Vest4

0.57

MVP

0.35

MPC

0.32

ClinPred

0.038

GERP RS

6.2

Varity_R

0.074

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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