rs10876550

chr12-54318524-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000553061.1(ENSG00000258344):n.546-26538G>A variant causes a intron, non coding transcript 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: ENST00000553061.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000553061.1	n.546-26538G>A		intron_variant, non_coding_transcript_variant		5
COPZ1	ENST00000552848.5	c.-81-6559G>A		intron_variant		5
COPZ1	ENST00000548076.5	n.161+17144G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.654

Alfa AF: 0.575 Hom.: 46730

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10876550; hg19: chr12-54712308;