1-160332508-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004371.4(COPA):c.436A>G(p.Thr146Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,416 control chromosomes in the GnomAD database, including 1,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 523 hom., cov: 31)

Exomes 𝑓: 0.0064 ( 516 hom. )

Consequence

COPA
NM_004371.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.44

Publications

11 publications found

Variant links:

Genes affected

COPA (HGNC:2230): (COPI coat complex subunit alpha) In eukaryotic cells, protein transport between the endoplasmic reticulum and Golgi compartments is mediated in part by non-clathrin-coated vesicular coat proteins (COPs). Seven coat proteins have been identified, and they represent subunits of a complex known as coatomer. The subunits are designated alpha-COP, beta-COP, beta-prime-COP, gamma-COP, delta-COP, epsilon-COP, and zeta-COP. The alpha-COP, encoded by COPA, shares high sequence similarity with RET1P, the alpha subunit of the coatomer complex in yeast. Also, the N-terminal 25 amino acids of alpha-COP encode the bioactive peptide, xenin, which stimulates exocrine pancreatic secretion and may act as a gastrointestinal hormone. Alternative splicing results in multiple splice forms encoding distinct isoforms. [provided by RefSeq, Jul 2008]

COPA Gene-Disease associations (from GenCC):

autoimmune interstitial lung disease-arthritis syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

COPA 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=0.0019013286).

BP6

Variant 1-160332508-T-C is Benign according to our data. Variant chr1-160332508-T-C is described in ClinVar as [Benign]. Clinvar id is 476028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPA	NM_004371.4 link	c.436A>G	p.Thr146Ala	missense_variant	Exon 6 of 33	ENST00000241704.8	NP_004362.2	P53621-1
COPA	NM_001098398.2 link	c.436A>G	p.Thr146Ala	missense_variant	Exon 6 of 33		NP_001091868.1	P53621-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8 link	c.436A>G	p.Thr146Ala	missense_variant	Exon 6 of 33	1	NM_004371.4	ENSP00000241704.7		P53621-1

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7094

AN:

151680

Hom.:

521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.0356

GnomAD2 exomes

AF:

0.0168

AC:

4213

AN:

251098

AF XY:

0.0126

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.0290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00979

GnomAD4 exome

AF:

0.00642

AC:

9378

AN:

1461618

Hom.:

516

Cov.:

AF XY:

0.00555

AC XY:

4036

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.162

AC:

5426

AN:

33444

American (AMR)

AF:

0.0279

AC:

1244

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0334

AC:

1327

AN:

39682

South Asian (SAS)

AF:

0.00109

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.0257

AC:

148

AN:

5768

European-Non Finnish (NFE)

AF:

0.000345

AC:

384

AN:

1111956

Other (OTH)

AF:

0.0124

AC:

751

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

396

793

1189

1586

1982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0468

AC:

7102

AN:

151798

Hom.:

523

Cov.:

AF XY:

0.0456

AC XY:

3381

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.157

AC:

6500

AN:

41304

American (AMR)

AF:

0.0214

AC:

326

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0251

AC:

130

AN:

5176

South Asian (SAS)

AF:

0.00291

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000633

AC:

AN:

67970

Other (OTH)

AF:

0.0367

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

290

580

869

1159

1449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0176

Hom.:

381

Bravo

AF:

0.0541

ESP6500AA

AF:

0.144

AC:

633

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0185

AC:

2242

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autoimmune interstitial lung disease-arthritis syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.082

.;T;.;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.53

T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

N;N;.;.

PhyloP100

3.4

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.5

N;N;.;.

REVEL

Benign

0.14

Sift

Benign

0.040

D;D;.;.

Sift4G

Benign

0.14

T;T;.;.

Polyphen

0.0010

B;B;.;.

Vest4

0.044

MPC

1.3

ClinPred

0.013

GERP RS

3.9

PromoterAI

0.0061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.11

Mutation Taster

=93/7

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