rs12914876

Positions:

• chr15-49146218-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004236.4(COPS2):​c.55-1140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,054 control chromosomes in the GnomAD database, including 2,118 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 (2118 hom., cov: 31)
• Consequence: COPS2 NM_004236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPS2	NM_004236.4	c.55-1140G>A		intron_variant		ENST00000388901.10	NP_004227.1
COPS2	NM_001143887.2	c.55-1140G>A		intron_variant			NP_001137359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPS2	ENST00000388901.10	c.55-1140G>A		intron_variant		1	NM_004236.4	ENSP00000373553	P4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22603 AN: 151936 Hom.: 2117 Cov.: 31

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 22597 AN: 152054 Hom.: 2118 Cov.: 31 AF XY: 0.146 AC XY: 10870 AN XY: 74334

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0708

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.153

Alfa AF: 0.191 Hom.: 586

Bravo AF: 0.141

Asia WGS AF: 0.0330 AC: 116 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.70

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: rs12914876; hg19: chr15-49438415;