rs6676805

Positions:

• chr1-175990492-G-C
• chr1-175990492-G-T

Variant summary

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

The NM_022457.7(COP1):​c.1730-1013C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,062 control chromosomes in the GnomAD database, including 1,859 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 0.14 (1859 hom., cov: 32)
• Consequence: COP1 NM_022457.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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]

COP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COP1	NM_022457.7	c.1730-1013C>G		intron_variant		ENST00000367669.8	NP_071902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COP1	ENST00000367669.8	c.1730-1013C>G		intron_variant		1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20864 AN: 151946 Hom.: 1858 Cov.: 32

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0948

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.137 AC: 20858 AN: 152062 Hom.: 1859 Cov.: 32 AF XY: 0.138 AC XY: 10269 AN XY: 74342

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.131

Alfa AF: 0.103 Hom.: 189

Bravo AF: 0.121

Asia WGS AF: 0.179 AC: 624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.28

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: rs6676805; hg19: chr1-175959628;