Genetic Variant COP1:p.Arg384Gln (chr1-176081278-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_022457.7(COP1):c.1151G>A(p.Arg384Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,570,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

COP1
NM_022457.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.24

Publications

4 publications found

Variant links:

Genes affected

COP1 (HGNC:17440): (COP1 E3 ubiquitin ligase) Enables ubiquitin protein ligase activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and response to ionizing radiation. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

COP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1314908).

BS2

High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022457.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COP1	NM_022457.7	MANE Select	c.1151G>A	p.Arg384Gln	missense	Exon 11 of 20	NP_071902.2
COP1	NM_001001740.4		c.1079G>A	p.Arg360Gln	missense	Exon 10 of 19	NP_001001740.1	Q8NHY2-2
COP1	NM_001286644.2		c.431G>A	p.Arg144Gln	missense	Exon 9 of 18	NP_001273573.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COP1	ENST00000367669.8	TSL:1 MANE Select	c.1151G>A	p.Arg384Gln	missense	Exon 11 of 20	ENSP00000356641.3	Q8NHY2-1
COP1	ENST00000308769.12	TSL:1	c.1079G>A	p.Arg360Gln	missense	Exon 10 of 19	ENSP00000310943.8	Q8NHY2-2
COP1	ENST00000367667.5	TSL:1	n.*327G>A		non_coding_transcript_exon	Exon 9 of 18	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes

AF:

0.0000760

AC:

AN:

144736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000698

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000120

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000152

AC:

AN:

230226

AF XY:

0.000184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000104

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.0000479

Gnomad NFE exome

AF:

0.000234

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.000205

AC:

292

AN:

1426172

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

152

AN XY:

709938

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31766

American (AMR)

AF:

0.000150

AC:

AN:

40130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25346

East Asian (EAS)

AF:

0.000306

AC:

AN:

39196

South Asian (SAS)

AF:

0.0000491

AC:

AN:

81404

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52688

Middle Eastern (MID)

AF:

0.00142

AC:

AN:

5618

European-Non Finnish (NFE)

AF:

0.000219

AC:

239

AN:

1091304

Other (OTH)

AF:

0.000358

AC:

AN:

58720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000760

AC:

AN:

144790

Hom.:

Cov.:

AF XY:

0.0000429

AC XY:

AN XY:

69898

show subpopulations

African (AFR)

AF:

0.0000256

AC:

AN:

39066

American (AMR)

AF:

0.0000697

AC:

AN:

14342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

4994

South Asian (SAS)

AF:

0.000217

AC:

AN:

4604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.000120

AC:

AN:

66868

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000223

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000206

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.028

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.2

PhyloP100

7.2

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.46

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.78

MVP

0.31

MPC

1.3

ClinPred

0.080

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.65

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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