rs142993682

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2BS2

The NM_001144061.2(COPB1):c.1699C>T(p.Arg567Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,752 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

COPB1
NM_001144061.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.71

Publications

6 publications found

Variant links:

Genes affected

COPB1 (HGNC:2231): (COPI coat complex subunit beta 1) This gene encodes a protein subunit of the coatomer complex associated with non-clathrin coated vesicles. The coatomer complex, also known as the coat protein complex 1, forms in the cytoplasm and is recruited to the Golgi by activated guanosine triphosphatases. Once at the Golgi membrane, the coatomer complex may assist in the movement of protein and lipid components back to the endoplasmic reticulum. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]

COPB1 Gene-Disease associations (from GenCC):

Baralle-Macken syndrome
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

COPB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.3822 (below the threshold of 3.09). Trascript score misZ: 2.5602 (below the threshold of 3.09). GenCC associations: The gene is linked to Baralle-Macken syndrome.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144061.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COPB1	NM_001144061.2	MANE Select	c.1699C>T	p.Arg567Cys	missense	Exon 14 of 22	NP_001137533.1	P53618
COPB1	NM_001144062.2		c.1699C>T	p.Arg567Cys	missense	Exon 14 of 22	NP_001137534.1	P53618
COPB1	NM_016451.5		c.1699C>T	p.Arg567Cys	missense	Exon 14 of 22	NP_057535.1	P53618

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COPB1	ENST00000439561.7	TSL:1 MANE Select	c.1699C>T	p.Arg567Cys	missense	Exon 14 of 22	ENSP00000397873.2	P53618
COPB1	ENST00000249923.7	TSL:1	c.1699C>T	p.Arg567Cys	missense	Exon 14 of 22	ENSP00000249923.3	P53618
COPB1	ENST00000890285.1		c.1807C>T	p.Arg603Cys	missense	Exon 15 of 23	ENSP00000560344.1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000251

AC:

AN:

251396

AF XY:

0.000302

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000181

AC:

264

AN:

1461542

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33474

American (AMR)

AF:

0.000492

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.000220

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000147

AC:

163

AN:

1111804

Other (OTH)

AF:

0.000398

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000158

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41536

American (AMR)

AF:

0.000458

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.000443

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

PhyloP100

9.7

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MVP

0.70

MPC

0.93

ClinPred

0.41

GERP RS

6.0

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.67

gMVP

0.75

Mutation Taster

=92/8

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