Genetic Variant NM_004236.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPS2	NM_004236.4 link	c.1187+83T>C		intron_variant	Intron 12 of 12	ENST00000388901.10	NP_004227.1	P61201-1
COPS2	NM_001143887.2 link	c.1208+83T>C		intron_variant	Intron 12 of 12		NP_001137359.1	P61201-2Q59EL2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COPS2	ENST00000388901.10 link	c.1187+83T>C	intron_variant	Intron 12 of 12	1	NM_004236.4	ENSP00000373553.5	P61201-1
COPS2	ENST00000299259.10 link	c.1208+83T>C	intron_variant	Intron 12 of 12	1		ENSP00000299259.6	P61201-2
COPS2	ENST00000542928.5 link	c.995+83T>C	intron_variant	Intron 10 of 10	2		ENSP00000443664.1	B4DIH5
COPS2	ENST00000560240.5 link	n.138+858T>C	intron_variant	Intron 2 of 3	4		ENSP00000453546.1	H0YMC2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over