Genetic Variant COPA:c.40+1076G>T (chr1-160342055-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004371.4(COPA):c.40+1076G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,054 control chromosomes in the GnomAD database, including 14,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14899 hom., cov: 32)

Consequence

COPA
NM_004371.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.245

Publications

16 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPA	NM_004371.4 link	c.40+1076G>T		intron_variant	Intron 1 of 32	ENST00000241704.8	NP_004362.2	P53621-1
COPA	NM_001098398.2 link	c.40+1076G>T		intron_variant	Intron 1 of 32		NP_001091868.1	P53621-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8 link	c.40+1076G>T		intron_variant	Intron 1 of 32	1	NM_004371.4	ENSP00000241704.7		P53621-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

65083

AN:

151936

Hom.:

14903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.611

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.428

AC:

65102

AN:

152054

Hom.:

14899

Cov.:

AF XY:

0.430

AC XY:

31976

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.257

AC:

10634

AN:

41458

American (AMR)

AF:

0.469

AC:

7156

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1465

AN:

3472

East Asian (EAS)

AF:

0.343

AC:

1772

AN:

5172

South Asian (SAS)

AF:

0.610

AC:

2936

AN:

4814

European-Finnish (FIN)

AF:

0.499

AC:

5277

AN:

10572

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34243

AN:

67978

Other (OTH)

AF:

0.462

AC:

974

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1805

3609

5414

7218

9023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.486

Hom.:

9414

Bravo

AF:

0.418

Asia WGS

AF:

0.474

AC:

1647

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.7

(source)

DANN

Benign

0.60

PhyloP100

-0.24

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over