1-160342475-T-G

Variant names:

• chr1-160342475-T-G
• rs10752637
• NM_004371.4:c.40+656A>C

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+656A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,004 control chromosomes in the GnomAD database, including 32,982 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 0.64 (32982 hom., cov: 31)
• Consequence: COPA NM_004371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 22 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPA	NM_004371.4	c.40+656A>C		intron_variant	Intron 1 of 32	ENST00000241704.8	NP_004362.2
COPA	NM_001098398.2	c.40+656A>C		intron_variant	Intron 1 of 32		NP_001091868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8	c.40+656A>C		intron_variant	Intron 1 of 32	1	NM_004371.4	ENSP00000241704.7

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97680 AN: 151886 Hom.: 32934 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.643 AC: 97787 AN: 152004 Hom.: 32982 Cov.: 31 AF XY: 0.640 AC XY: 47544 AN XY: 74278

African (AFR) AF: 0.864 AC: 35818 AN: 41478

American (AMR) AF: 0.575 AC: 8776 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3472

East Asian (EAS) AF: 0.464 AC: 2398 AN: 5172

South Asian (SAS) AF: 0.704 AC: 3389 AN: 4814

European-Finnish (FIN) AF: 0.550 AC: 5796 AN: 10534

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37769 AN: 67966

Other (OTH) AF: 0.641 AC: 1353 AN: 2110

Alfa AF: 0.598 Hom.: 41324

Bravo AF: 0.654

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10752637; hg19: chr1-160312265;