rs10876550

Variant names:

• chr12-54318524-G-A
• rs10876550
• ENST00000552848.5:c.-81-6559G>A

Variant summary

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

The ENST00000552848.5(COPZ1):​c.-81-6559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,662 control chromosomes in the GnomAD database, including 36,596 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 0.68 (36596 hom., cov: 30)
• Consequence: COPZ1 ENST00000552848.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 33 publications found

Genes affected

COPZ1 (HGNC:2243): (COPI coat complex subunit zeta 1) This gene encodes a subunit of the cytoplasmic coatamer protein complex, which is involved in autophagy and intracellular protein trafficking. The coatomer protein complex is comprised of seven subunits and functions as the coat protein of coat protein complex (COP)I-vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ENSG00000258344 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPZ1	ENST00000552848.5	c.-81-6559G>A		intron_variant	Intron 1 of 5	5		ENSP00000449414.1
COPZ1	ENST00000548076.5	n.161+17144G>A		intron_variant	Intron 1 of 3	5
ENSG00000258344	ENST00000553061.1	n.546-26538G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103042 AN: 151544 Hom.: 36534 Cov.: 30

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.680 AC: 103164 AN: 151662 Hom.: 36596 Cov.: 30 AF XY: 0.686 AC XY: 50805 AN XY: 74100

African (AFR) AF: 0.873 AC: 36169 AN: 41434

American (AMR) AF: 0.710 AC: 10761 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3426 AN: 5160

South Asian (SAS) AF: 0.758 AC: 3653 AN: 4820

European-Finnish (FIN) AF: 0.689 AC: 7153 AN: 10382

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38225 AN: 67924

Other (OTH) AF: 0.654 AC: 1379 AN: 2108

Alfa AF: 0.597 Hom.: 116344

Bravo AF: 0.686

Asia WGS AF: 0.773 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.15
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10876550; hg19: chr12-54712308;