1-176081294-GAAAAAAA-GAAAAAAAA

Variant names:

• chr1-176081294-G-GA
• rs56720201
• NM_022457.7:c.1142-8dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_022457.7(COP1):​c.1142-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 1,255,060 control chromosomes in the GnomAD database, including 117 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (96 hom., cov: 30)
  • Exomes 𝑓: 0.087 (21 hom.)
• Consequence: COP1 NM_022457.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COP1	NM_022457.7	c.1142-8dupT		splice_region_variant, intron_variant	Intron 10 of 19	ENST00000367669.8	NP_071902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COP1	ENST00000367669.8	c.1142-8_1142-7insT		splice_region_variant, intron_variant	Intron 10 of 19	1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 4477 AN: 90862 Hom.: 96 Cov.: 30

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.0485

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0390

Gnomad EAS AF: 0.00434

Gnomad SAS AF: 0.0301

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0508

GnomAD4 exome AF: 0.0865 AC: 100711 AN: 1164190 Hom.: 21 Cov.: 0 AF XY: 0.0854 AC XY: 49417 AN XY: 578344

Gnomad4 AFR exome AF: 0.0721

Gnomad4 AMR exome AF: 0.0665

Gnomad4 ASJ exome AF: 0.0661

Gnomad4 EAS exome AF: 0.0492

Gnomad4 SAS exome AF: 0.0784

Gnomad4 FIN exome AF: 0.0763

Gnomad4 NFE exome AF: 0.0910

Gnomad4 OTH exome AF: 0.0771

GnomAD4 genome AF: 0.0493 AC: 4483 AN: 90870 Hom.: 96 Cov.: 30 AF XY: 0.0501 AC XY: 2120 AN XY: 42302

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.0390

Gnomad4 EAS AF: 0.00436

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.0840

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs56720201; hg19: chr1-176050430;