chr15-49128619-A-G

Variant names:

• chr15-49128619-A-G
• rs17394420
• NM_004236.4:c.1187+83T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777
• Publications: 7 publications found

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]

ACMG classification

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

Selected	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
	COPS2	NM_001143887.2		c.1208+83T>C		intron	N/A	NP_001137359.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPS2	ENST00000388901.10	TSL:1 MANE Select	c.1187+83T>C		intron	N/A	ENSP00000373553.5
	COPS2	ENST00000299259.10	TSL:1	c.1208+83T>C		intron	N/A	ENSP00000299259.6
	COPS2	ENST00000542928.5	TSL:2	c.995+83T>C		intron	N/A	ENSP00000443664.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23150 AN: 152096 Hom.: 2262 Cov.: 32

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

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: 26 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

GnomAD4 genome AF: 0.152 AC: 23143 AN: 152214 Hom.: 2260 Cov.: 32 AF XY: 0.154 AC XY: 11473 AN XY: 74412

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: 25 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: 55 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14179 AN: 67984

Other (OTH) AF: 0.183 AC: 386 AN: 2110

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	12
DANN	Benign	0.47
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17394420; hg19: chr15-49420816;