rs12231393

Variant names:

• chr12-54318989-T-C
• rs12231393
• ENST00000552848.5:c.-81-6094T>C

Variant summary

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

The ENST00000552848.5(COPZ1):​c.-81-6094T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,220 control chromosomes in the GnomAD database, including 1,660 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 0.14 (1660 hom., cov: 32)
• Consequence: COPZ1 ENST00000552848.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 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.-81-6094T>C		intron_variant	Intron 1 of 5	5		ENSP00000449414.1
COPZ1	ENST00000548076.5	n.161+17609T>C		intron_variant	Intron 1 of 3	5
ENSG00000258344	ENST00000553061.1	n.546-26073T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21096 AN: 152102 Hom.: 1655 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.139 AC: 21124 AN: 152220 Hom.: 1660 Cov.: 32 AF XY: 0.146 AC XY: 10829 AN XY: 74422

African (AFR) AF: 0.111 AC: 4622 AN: 41550

American (AMR) AF: 0.202 AC: 3089 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1244 AN: 5194

South Asian (SAS) AF: 0.139 AC: 670 AN: 4822

European-Finnish (FIN) AF: 0.227 AC: 2405 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8508 AN: 68014

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.125 Hom.: 672

Bravo AF: 0.134

Asia WGS AF: 0.226 AC: 783 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.83
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs12231393; hg19: chr12-54712773;