NM_022457.7:c.1767A>G

Variant names:

• chr1-175989442-T-C
• rs111531372
• NM_022457.7:c.1767A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_022457.7(COP1):​c.1767A>G​(p.Lys589Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,607,570 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (2 hom.)
• Consequence: COP1 NM_022457.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.250
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-175989442-T-C is Benign according to our data. Variant chr1-175989442-T-C is described in ClinVar as Benign. ClinVar VariationId is 715553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.25 with no splicing effect.
• BS2: High AC in GnomAd4 at 400 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COP1	NM_022457.7	MANE Select	c.1767A>G	p.Lys589Lys	synonymous	Exon 16 of 20	NP_071902.2
	COP1	NM_001001740.4		c.1695A>G	p.Lys565Lys	synonymous	Exon 15 of 19	NP_001001740.1	Q8NHY2-2
	COP1	NM_001286644.2		c.1047A>G	p.Lys349Lys	synonymous	Exon 14 of 18	NP_001273573.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COP1	ENST00000367669.8	TSL:1 MANE Select	c.1767A>G	p.Lys589Lys	synonymous	Exon 16 of 20	ENSP00000356641.3	Q8NHY2-1
	COP1	ENST00000308769.12	TSL:1	c.1695A>G	p.Lys565Lys	synonymous	Exon 15 of 19	ENSP00000310943.8	Q8NHY2-2
	COP1	ENST00000367667.5	TSL:1	n.*943A>G		non_coding_transcript_exon	Exon 14 of 18	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152206 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000651 AC: 163 AN: 250444 AF XY: 0.000487

Gnomad AFR exome AF: 0.00895

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000286 AC: 416 AN: 1455246 Hom.: 2 Cov.: 27 AF XY: 0.000242 AC XY: 175 AN XY: 724440

African (AFR) AF: 0.00975 AC: 325 AN: 33332

American (AMR) AF: 0.000291 AC: 13 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5752

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1106038

Other (OTH) AF: 0.000914 AC: 55 AN: 60178

GnomAD4 genome AF: 0.00263 AC: 400 AN: 152324 Hom.: 3 Cov.: 32 AF XY: 0.00260 AC XY: 194 AN XY: 74492

African (AFR) AF: 0.00919 AC: 382 AN: 41582

American (AMR) AF: 0.000980 AC: 15 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00160 Hom.: 1

Bravo AF: 0.00331

Asia WGS AF: 0.00346 AC: 12 AN: 3478

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	-0.52
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		0.25
Mutation Taster		=99/1	polymorphism

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: rs111531372; hg19: chr1-175958578;