rs11170877

chr12-54340505-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BA1

The ENST00000549043.5(COPZ1):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,611,242 control chromosomes in the GnomAD database, including 15,917 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 0.17 (2371 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13546 hom.)
• Consequence: COPZ1 ENST00000549043.5 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COPZ1	NM_016057.3	c.19-42A>G		intron_variant		ENST00000262061.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPZ1	ENST00000262061.7	c.19-42A>G		intron_variant		1	NM_016057.3	P1
	ENST00000553061.1	n.546-4557A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25195 AN: 151922 Hom.: 2357 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.141

GnomAD3 exomes AF: 0.156 AC: 38821 AN: 248782 Hom.: 3587 AF XY: 0.149 AC XY: 19997 AN XY: 134580

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.0692

Gnomad EAS exome AF: 0.227

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.129 AC: 187628 AN: 1459202 Hom.: 13546 Cov.: 31 AF XY: 0.127 AC XY: 92332 AN XY: 725982

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.0708

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.166 AC: 25247 AN: 152040 Hom.: 2371 Cov.: 31 AF XY: 0.172 AC XY: 12800 AN XY: 74314

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.145

Alfa AF: 0.117 Hom.: 2038

Bravo AF: 0.166

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.117 AC: 451

ESP6500AA AF: 0.231 AC: 1016

ESP6500EA AF: 0.111 AC: 958

ExAC AF: 0.152 AC: 18515

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	13
Dann	Benign	0.82
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.00038	N
LIST_S2	Uncertain	0.90	D;D
MetaRNN	Benign	0.0044	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.17	T;T
Vest4		0.057
ClinPred		0.017	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.44

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: rs11170877; hg19: chr12-54734289; COSMIC: COSV50432095; COSMIC: COSV50432095;