dbSNP rs17394420: COPS2:c.1187+83T>C (chr15-49128619-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_004236.4(COPS2):c.1187+83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 956,810 control chromosomes in the GnomAD database, including 18,661 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 0.15 ( 2260 hom., cov: 32)

Exomes 𝑓: 0.19 ( 16401 hom. )

Consequence

COPS2
NM_004236.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.777

Publications

7 publications found

Variant links:

Genes affected

COPS2 (HGNC:30747): (COP9 signalosome subunit 2) Predicted to enable transcription corepressor activity. Involved in protein deneddylation and protein phosphorylation. Located in cytoplasm. Part of COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

COPS2 links:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPS2	NM_004236.4	MANE Select	c.1187+83T>C		intron	N/A	NP_004227.1	P61201-1
	COPS2	NM_001143887.2		c.1208+83T>C		intron	N/A	NP_001137359.1	P61201-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COPS2	ENST00000388901.10	TSL:1 MANE Select	c.1187+83T>C	intron	N/A	ENSP00000373553.5	P61201-1
COPS2	ENST00000299259.10	TSL:1	c.1208+83T>C	intron	N/A	ENSP00000299259.6	P61201-2
COPS2	ENST00000940241.1		c.1205+83T>C	intron	N/A	ENSP00000610300.1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23150

AN:

152096

Hom.:

2262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.192

AC:

154188

AN:

804596

Hom.:

16401

AF XY:

0.194

AC XY:

81358

AN XY:

419490

show subpopulations

African (AFR)

AF:

0.0357

AC:

668

AN:

18686

American (AMR)

AF:

0.115

AC:

3318

AN:

28762

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

4055

AN:

18366

East Asian (EAS)

AF:

0.000754

AC:

AN:

34462

South Asian (SAS)

AF:

0.197

AC:

11167

AN:

56574

European-Finnish (FIN)

AF:

0.250

AC:

12463

AN:

49914

Middle Eastern (MID)

AF:

0.280

AC:

1153

AN:

4124

European-Non Finnish (NFE)

AF:

0.205

AC:

114190

AN:

556052

Other (OTH)

AF:

0.190

AC:

7148

AN:

37656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5750

11500

17251

23001

28751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2666

5332

7998

10664

13330

<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:

0.152

AC:

23143

AN:

152214

Hom.:

2260

Cov.:

AF XY:

0.154

AC XY:

11473

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0404

AC:

1679

AN:

41564

American (AMR)

AF:

0.160

AC:

2444

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

773

AN:

3470

East Asian (EAS)

AF:

0.00482

AC:

AN:

5190

South Asian (SAS)

AF:

0.180

AC:

869

AN:

4824

European-Finnish (FIN)

AF:

0.247

AC:

2612

AN:

10580

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14179

AN:

67984

Other (OTH)

AF:

0.183

AC:

386

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

974

1948

2921

3895

4869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.176

Hom.:

464

Bravo

AF:

0.140

Asia WGS

AF:

0.0790

AC:

274

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.47

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(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

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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