Genetic Variant COPZ1:c.169+399A>G (chr12-54342686-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016057.3(COPZ1):c.169+399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 198,002 control chromosomes in the GnomAD database, including 45,248 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 ( 36408 hom., cov: 29)

Exomes 𝑓: 0.60 ( 8840 hom. )

Consequence

COPZ1
NM_016057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.114

Variant links:

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]

COPZ1 links:

ENSG00000258344 (HGNC:):

ENSG00000258344 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPZ1	NM_016057.3 link	c.169+399A>G		intron_variant	Intron 3 of 8	ENST00000262061.7	NP_057141.1	P61923-1A0A024RB72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPZ1	ENST00000262061.7 link	c.169+399A>G		intron_variant	Intron 3 of 8	1	NM_016057.3	ENSP00000262061.2		P61923-1

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

102981

AN:

151672

Hom.:

36344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.761

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.645

GnomAD4 exome

AF:

0.598

AC:

27650

AN:

46210

Hom.:

8840

AF XY:

0.604

AC XY:

14653

AN XY:

24242

show subpopulations

Gnomad4 AFR exome

AF:

0.879

Gnomad4 AMR exome

AF:

0.721

Gnomad4 ASJ exome

AF:

0.465

Gnomad4 EAS exome

AF:

0.627

Gnomad4 SAS exome

AF:

0.728

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.599

GnomAD4 genome

AF:

0.679

AC:

103104

AN:

151792

Hom.:

36408

Cov.:

AF XY:

0.684

AC XY:

50764

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.862

Gnomad4 AMR

AF:

0.707

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.664

Gnomad4 SAS

AF:

0.760

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.569

Gnomad4 OTH

AF:

0.643

Alfa

AF:

0.584

Hom.:

34820

Bravo

AF:

0.684

Asia WGS

AF:

0.777

AC:

2701

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.61

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over