rs2147471

Variant names:

• chr1-160342055-C-A
• rs2147471
• NM_004371.4:c.40+1076G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 16 publications found

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)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004371.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPA	NM_004371.4	MANE Select	c.40+1076G>T		intron	N/A	NP_004362.2
	COPA	NM_001098398.2		c.40+1076G>T		intron	N/A	NP_001091868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPA	ENST00000241704.8	TSL:1 MANE Select	c.40+1076G>T		intron	N/A	ENSP00000241704.7
	COPA	ENST00000368069.7	TSL:1	c.40+1076G>T		intron	N/A	ENSP00000357048.3
	COPA	ENST00000971414.1		c.40+1076G>T		intron	N/A	ENSP00000641473.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65083 AN: 151936 Hom.: 14903 Cov.: 32

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.: 32 AF XY: 0.430 AC XY: 31976 AN XY: 74326

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2147471; hg19: chr1-160311845;