1-160342835-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPA	NM_004371.4	c.40+296G>A		intron_variant		ENST00000241704.8
COPA	NM_001098398.2	c.40+296G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPA	ENST00000241704.8	c.40+296G>A		intron_variant		1	NM_004371.4	P1

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

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.0765

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.0920

Gnomad4 SAS AF: 0.0887

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0509

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0755 Hom.: 986

Bravo AF: 0.161

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.25
Dann	Benign	0.39

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: rs1324738; hg19: chr1-160312625;