1-160342835-C-T

Variant names:

• chr1-160342835-C-T
• rs1324738
• NM_004371.4:c.40+296G>A

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+296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,006 control chromosomes in the GnomAD database, including 3,397 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 0.15 (3397 hom., cov: 31)
• Consequence: COPA NM_004371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.70
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPA	NM_004371.4	MANE Select	c.40+296G>A		intron	N/A	NP_004362.2
	COPA	NM_001098398.2		c.40+296G>A		intron	N/A	NP_001091868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPA	ENST00000241704.8	TSL:1 MANE Select	c.40+296G>A		intron	N/A	ENSP00000241704.7
	COPA	ENST00000368069.7	TSL:1	c.40+296G>A		intron	N/A	ENSP00000357048.3
	COPA	ENST00000647683.1		c.40+296G>A		intron	N/A	ENSP00000497495.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22726 AN: 151888 Hom.: 3375 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.150 AC: 22796 AN: 152006 Hom.: 3397 Cov.: 31 AF XY: 0.147 AC XY: 10929 AN XY: 74324

African (AFR) AF: 0.389 AC: 16080 AN: 41376

American (AMR) AF: 0.0765 AC: 1169 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 278 AN: 3468

East Asian (EAS) AF: 0.0920 AC: 476 AN: 5176

South Asian (SAS) AF: 0.0887 AC: 428 AN: 4826

European-Finnish (FIN) AF: 0.0524 AC: 554 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0509 AC: 3461 AN: 67984

Other (OTH) AF: 0.123 AC: 260 AN: 2108

Alfa AF: 0.0885 Hom.: 1945

Bravo AF: 0.161

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.25
DANN	Benign	0.39
PhyloP100		-3.7
PromoterAI		-0.018	Neutral
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: rs1324738; hg19: chr1-160312625;