rs11587785

Positions:

• chr1-176167350-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022457.7(COP1):​c.566-3459C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,280 control chromosomes in the GnomAD database, including 117 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 0.033 (117 hom., cov: 32)
• Consequence: COP1 NM_022457.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

Genes affected

COP1 (HGNC:17440): (COP1 E3 ubiquitin ligase) Enables ubiquitin protein ligase activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and response to ionizing radiation. Part of Cul4A-RING E3 ubiquitin ligase complex. [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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0327 (4972/152280) while in subpopulation NFE AF= 0.0473 (3216/68036). AF 95% confidence interval is 0.0459. There are 117 homozygotes in gnomad4. There are 2435 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4972 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COP1	NM_022457.7	c.566-3459C>A		intron_variant		ENST00000367669.8	NP_071902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COP1	ENST00000367669.8	c.566-3459C>A		intron_variant		1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4978 AN: 152162 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0327 AC: 4972 AN: 152280 Hom.: 117 Cov.: 32 AF XY: 0.0327 AC XY: 2435 AN XY: 74456

Gnomad4 AFR AF: 0.00751

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0385 Hom.: 20

Bravo AF: 0.0299

Asia WGS AF: 0.0260 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.84

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: rs11587785; hg19: chr1-176136486;