chr1-175990492-G-C

Variant names:

• chr1-175990492-G-C
• rs6676805
• NM_022457.7:c.1730-1013C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022457.7. 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
	COP1	NM_022457.7	MANE Select	c.1730-1013C>G		intron	N/A	NP_071902.2
	COP1	NM_001001740.4		c.1658-1013C>G		intron	N/A	NP_001001740.1
	COP1	NM_001286644.2		c.1010-1013C>G		intron	N/A	NP_001273573.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COP1	ENST00000367669.8	TSL:1 MANE Select	c.1730-1013C>G		intron	N/A	ENSP00000356641.3
	COP1	ENST00000308769.12	TSL:1	c.1658-1013C>G		intron	N/A	ENSP00000310943.8
	COP1	ENST00000367667.5	TSL:1	n.*906-1013C>G		intron	N/A	ENSP00000356639.1

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

African (AFR) AF: 0.0301 AC: 1248 AN: 41522

American (AMR) AF: 0.0948 AC: 1448 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1620 AN: 5172

South Asian (SAS) AF: 0.175 AC: 841 AN: 4810

European-Finnish (FIN) AF: 0.213 AC: 2254 AN: 10570

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12516 AN: 67928

Other (OTH) AF: 0.131 AC: 275 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		0.23
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: rs6676805; hg19: chr1-175959628;