rs79304843

chr1-160299191-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_004371.4(COPA):c.1741C>T(p.Leu581=) 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
• Clinical Significance: Benign criteria provided, single submitter B:3 O:1
• Conservation: PhyloP100: 4.35

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]

ACMG classification

Verdict is Benign. Variant got -12 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_single_submitter, 1 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. This position pass quality control queck.
• BS2: High AC in GnomAd at 3870 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPA	NM_004371.4	c.1741C>T	p.Leu581=	synonymous_variant	18/33	ENST00000241704.8
COPA	NM_001098398.2	c.1768C>T	p.Leu590=	synonymous_variant	18/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPA	ENST00000241704.8	c.1741C>T	p.Leu581=	synonymous_variant	18/33	1	NM_004371.4	P1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3870 AN: 152128 Hom.: 51 Cov.: 32

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.: 96 AF XY: 0.0268 AC XY: 3643 AN XY: 135906

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.: 33 AF XY: 0.0320 AC XY: 23269 AN XY: 727238

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.: 51 Cov.: 32 AF XY: 0.0242 AC XY: 1802 AN XY: 74434

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.: 35

Bravo AF: 0.0249

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.0364

EpiControl AF: 0.0350

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Autoimmune interstitial lung disease-arthritis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs79304843; hg19: chr1-160268981;