rs11170877

Variant names:

• chr12-54340505-A-G
• rs11170877
• ENST00000549043.5:c.1A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_Supporting 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
• Publications: 18 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 -7 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 9 codons. Genomic position: 54340529. Lost 0.045 part of the original CDS.
• 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 rank	MANE	Protein	UniProt
COPZ1	NM_016057.3	c.19-42A>G		intron_variant	Intron 1 of 8	ENST00000262061.7	NP_057141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPZ1	ENST00000262061.7	c.19-42A>G		intron_variant	Intron 1 of 8	1	NM_016057.3	ENSP00000262061.2

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

GnomAD2 exomes AF: 0.156 AC: 38821 AN: 248782 AF XY: 0.149

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 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

African (AFR) AF: 0.233 AC: 7798 AN: 33398

American (AMR) AF: 0.242 AC: 10650 AN: 43996

Ashkenazi Jewish (ASJ) AF: 0.0708 AC: 1844 AN: 26032

East Asian (EAS) AF: 0.255 AC: 10103 AN: 39564

South Asian (SAS) AF: 0.132 AC: 11352 AN: 85776

European-Finnish (FIN) AF: 0.190 AC: 10148 AN: 53372

Middle Eastern (MID) AF: 0.0506 AC: 291 AN: 5756

European-Non Finnish (NFE) AF: 0.115 AC: 127571 AN: 1111074

Other (OTH) AF: 0.131 AC: 7871 AN: 60234

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

African (AFR) AF: 0.233 AC: 9670 AN: 41464

American (AMR) AF: 0.210 AC: 3203 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1205 AN: 5158

South Asian (SAS) AF: 0.140 AC: 675 AN: 4814

European-Finnish (FIN) AF: 0.213 AC: 2253 AN: 10582

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7629 AN: 67964

Other (OTH) AF: 0.145 AC: 305 AN: 2110

Alfa AF: 0.127 Hom.: 4059

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
DEOGEN2	Benign	0.0074	.;T
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
PhyloP100		0.18
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
PromoterAI		-0.0012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.44
Mutation Taster		=191/9	polymorphism (auto)

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

Other links and lift over

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