chr15-49133803-C-T

Variant names:

• chr15-49133803-C-T
• rs148364582
• NM_004236.4:c.903G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004236.4(COPS2):​c.903G>A​(p.Pro301Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00056 in 1,597,404 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: COPS2 NM_004236.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 15-49133803-C-T is Benign according to our data. Variant chr15-49133803-C-T is described in ClinVar as Benign. ClinVar VariationId is 788586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.436 with no splicing effect.
• BS2: High AC in GnomAd4 at 458 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPS2	NM_004236.4	MANE Select	c.903G>A	p.Pro301Pro	synonymous	Exon 9 of 13	NP_004227.1	P61201-1
	COPS2	NM_001143887.2		c.924G>A	p.Pro308Pro	synonymous	Exon 9 of 13	NP_001137359.1	P61201-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPS2	ENST00000388901.10	TSL:1 MANE Select	c.903G>A	p.Pro301Pro	synonymous	Exon 9 of 13	ENSP00000373553.5	P61201-1
	COPS2	ENST00000299259.10	TSL:1	c.924G>A	p.Pro308Pro	synonymous	Exon 9 of 13	ENSP00000299259.6	P61201-2
	COPS2	ENST00000940241.1		c.924G>A	p.Pro308Pro	synonymous	Exon 9 of 13	ENSP00000610300.1

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 459 AN: 151988 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000811 AC: 192 AN: 236728 AF XY: 0.000687

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.000192

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000550

Gnomad OTH exome AF: 0.000349

GnomAD4 exome AF: 0.000302 AC: 436 AN: 1445298 Hom.: 2 Cov.: 29 AF XY: 0.000298 AC XY: 214 AN XY: 718588

African (AFR) AF: 0.0114 AC: 371 AN: 32468

American (AMR) AF: 0.000291 AC: 12 AN: 41308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25564

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39424

South Asian (SAS) AF: 0.00 AC: 0 AN: 82344

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.0000217 AC: 24 AN: 1105904

Other (OTH) AF: 0.000435 AC: 26 AN: 59720

GnomAD4 genome AF: 0.00301 AC: 458 AN: 152106 Hom.: 2 Cov.: 33 AF XY: 0.00297 AC XY: 221 AN XY: 74366

African (AFR) AF: 0.0104 AC: 432 AN: 41490

American (AMR) AF: 0.000982 AC: 15 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00150 Hom.: 2

Bravo AF: 0.00343

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.44
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148364582; hg19: chr15-49426000; COSMIC: COSV54646159; COSMIC: COSV54646159;