Genetic Variant NM_016057.3:c.169+399A>G (chr12-54342686-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

15 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COPZ1	NM_016057.3	MANE Select	c.169+399A>G	intron	N/A	NP_057141.1	P61923-1
COPZ1	NM_001271736.2		c.193+399A>G	intron	N/A	NP_001258665.1	P61923-4
COPZ1	NM_001271735.2		c.169+399A>G	intron	N/A	NP_001258664.1	P61923-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COPZ1	ENST00000262061.7	TSL:1 MANE Select	c.169+399A>G	intron	N/A	ENSP00000262061.2	P61923-1
COPZ1	ENST00000549043.5	TSL:1	c.193+399A>G	intron	N/A	ENSP00000449270.1	P61923-4
COPZ1	ENST00000550027.5	TSL:1	n.194+399A>G	intron	N/A

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

African (AFR)

AF:

0.879

AC:

786

AN:

894

American (AMR)

AF:

0.721

AC:

2065

AN:

2864

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

538

AN:

1156

East Asian (EAS)

AF:

0.627

AC:

1073

AN:

1712

South Asian (SAS)

AF:

0.728

AC:

4333

AN:

5956

European-Finnish (FIN)

AF:

0.664

AC:

1308

AN:

1970

Middle Eastern (MID)

AF:

0.527

AC:

AN:

188

European-Non Finnish (NFE)

AF:

0.550

AC:

15910

AN:

28902

Other (OTH)

AF:

0.599

AC:

1538

AN:

2568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

502

1003

1505

2006

2508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.679

AC:

103104

AN:

151792

Hom.:

36408

Cov.:

AF XY:

0.684

AC XY:

50764

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.862

AC:

35650

AN:

41380

American (AMR)

AF:

0.707

AC:

10774

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1773

AN:

3470

East Asian (EAS)

AF:

0.664

AC:

3424

AN:

5156

South Asian (SAS)

AF:

0.760

AC:

3659

AN:

4814

European-Finnish (FIN)

AF:

0.689

AC:

7251

AN:

10526

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38604

AN:

67896

Other (OTH)

AF:

0.643

AC:

1355

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1544

3088

4631

6175

7719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.596

Hom.:

46254

Bravo

AF:

0.684

Asia WGS

AF:

0.777

AC:

2701

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.61

(source)

DANN

Benign

0.41

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over