15-49146129-T-C

Variant names:

• chr15-49146129-T-C
• rs12915792
• NM_004236.4:c.55-1051A>G

Variant summary

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

The NM_004236.4(COPS2):​c.55-1051A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,110 control chromosomes in the GnomAD database, including 54,704 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 0.84 (54704 hom., cov: 32)
• Consequence: COPS2 NM_004236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 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.55-1051A>G		intron	N/A	NP_004227.1
	COPS2	NM_001143887.2		c.55-1051A>G		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.55-1051A>G		intron	N/A	ENSP00000373553.5
	COPS2	ENST00000299259.10	TSL:1	c.55-1051A>G		intron	N/A	ENSP00000299259.6
	COPS2	ENST00000558843.5	TSL:1	c.55-1051A>G		intron	N/A	ENSP00000452944.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127556 AN: 151990 Hom.: 54666 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.839 AC: 127645 AN: 152110 Hom.: 54704 Cov.: 32 AF XY: 0.840 AC XY: 62499 AN XY: 74362

African (AFR) AF: 0.654 AC: 27096 AN: 41460

American (AMR) AF: 0.897 AC: 13693 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3303 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3888 AN: 5172

South Asian (SAS) AF: 0.786 AC: 3792 AN: 4822

European-Finnish (FIN) AF: 0.945 AC: 10028 AN: 10612

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62888 AN: 67982

Other (OTH) AF: 0.882 AC: 1862 AN: 2112

Alfa AF: 0.897 Hom.: 26932

Bravo AF: 0.830

Asia WGS AF: 0.765 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.97
DANN	Benign	0.41
PhyloP100		-0.17
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: rs12915792; hg19: chr15-49438326;