rs12231393

Positions:

• chr12-54318989-T-C

Variant summary

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

The ENST00000553061.1(ENSG00000258344):​n.546-26073T>C 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 0.139 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: ENST00000553061.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000553061.1	n.546-26073T>C		intron_variant, non_coding_transcript_variant		5
COPZ1	ENST00000552848.5	c.-81-6094T>C		intron_variant		5
COPZ1	ENST00000548076.5	n.161+17609T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.127

Alfa AF: 0.125 Hom.: 603

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12231393; hg19: chr12-54712773;