chr15-49128619-A-G

Position:

• chr15-49128619-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
COPS2	NM_004236.4	c.1187+83T>C		intron_variant		ENST00000388901.10
COPS2	NM_001143887.2	c.1208+83T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COPS2	ENST00000388901.10	c.1187+83T>C		intron_variant		1	NM_004236.4	P4
COPS2	ENST00000299259.10	c.1208+83T>C		intron_variant		1		A1
COPS2	ENST00000542928.5	c.995+83T>C		intron_variant		2
COPS2	ENST00000560240.5	c.138+858T>C		intron_variant, NMD_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.0357

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.000754

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.190

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

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.183

Alfa AF: 0.180 Hom.: 461

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	12
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs17394420; hg19: chr15-49420816;