rs79304843

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_004371.4(COPA):c.1741C>T(p.Leu581Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0311 in 1,614,114 control chromosomes in the GnomAD database, including 875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 51 hom., cov: 32)

Exomes 𝑓: 0.032 ( 824 hom. )

Consequence

COPA
NM_004371.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 4.35

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 1-160299191-G-A is Benign according to our data. Variant chr1-160299191-G-A is described in ClinVar as [Benign]. Clinvar id is 476022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-160299191-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0254 (3871/152248) while in subpopulation NFE AF= 0.0344 (2340/68018). AF 95% confidence interval is 0.0332. There are 51 homozygotes in gnomad4. There are 1802 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3871 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPA	NM_004371.4 link	c.1741C>T	p.Leu581Leu	synonymous_variant	Exon 18 of 33	ENST00000241704.8	NP_004362.2	P53621-1
COPA	NM_001098398.2 link	c.1768C>T	p.Leu590Leu	synonymous_variant	Exon 18 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.1741C>T	p.Leu581Leu	synonymous_variant	Exon 18 of 33	1	NM_004371.4	ENSP00000241704.7		P53621-1

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3870

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0309

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0251

AC:

6324

AN:

251458

Hom.:

AF XY:

0.0268

AC XY:

3643

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0306

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0321

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.0336

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0317

AC:

46356

AN:

1461866

Hom.:

824

Cov.:

AF XY:

0.0320

AC XY:

23269

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0136

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0282

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.0349

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0254

AC:

3871

AN:

152248

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1802

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0311

Gnomad4 FIN

AF:

0.0204

Gnomad4 NFE

AF:

0.0344

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0302

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0364

EpiControl

AF:

0.0350

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over