rs17472989

Variant names:

• chr15-49132169-A-G
• rs17472989
• NM_004236.4:c.948-1353T>C

Variant summary

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

The NM_004236.4(COPS2):​c.948-1353T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,008 control chromosomes in the GnomAD database, including 5,949 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 0.25 (5949 hom., cov: 31)
• Consequence: COPS2 NM_004236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPS2	NM_004236.4	c.948-1353T>C		intron_variant	Intron 9 of 12	ENST00000388901.10	NP_004227.1
COPS2	NM_001143887.2	c.969-1353T>C		intron_variant	Intron 9 of 12		NP_001137359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPS2	ENST00000388901.10	c.948-1353T>C		intron_variant	Intron 9 of 12	1	NM_004236.4	ENSP00000373553.5
COPS2	ENST00000299259.10	c.969-1353T>C		intron_variant	Intron 9 of 12	1		ENSP00000299259.6
COPS2	ENST00000542928.5	c.756-1353T>C		intron_variant	Intron 7 of 10	2		ENSP00000443664.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38119 AN: 151890 Hom.: 5948 Cov.: 31

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.251 AC: 38109 AN: 152008 Hom.: 5949 Cov.: 31 AF XY: 0.250 AC XY: 18573 AN XY: 74292

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.251

Alfa AF: 0.299 Hom.: 955

Bravo AF: 0.237

Asia WGS AF: 0.151 AC: 522 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.3
DANN	Benign	0.56

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: rs17472989; hg19: chr15-49424366;