1-176081294-GAAAAAAAA-GAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_022457.7(COP1):​c.1142-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 90,924 control chromosomes in the GnomAD database, including 16 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 0.016 (16 hom., cov: 30)
  • Exomes 𝑓: 0.28 (3 hom.)
  • Failed GnomAD Quality Control
• 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0165 (1496/90924) while in subpopulation AFR AF= 0.0459 (1107/24106). AF 95% confidence interval is 0.0437. There are 16 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1496 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 1495 AN: 90916 Hom.: 16 Cov.: 30

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.0139

Gnomad EAS AF: 0.00467

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.00523

Gnomad MID AF: 0.0234

Gnomad NFE AF: 0.00402

Gnomad OTH AF: 0.0169

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.281 AC: 299729 AN: 1065664 Hom.: 3 Cov.: 0 AF XY: 0.282 AC XY: 149119 AN XY: 529004

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.0165 AC: 1496 AN: 90924 Hom.: 16 Cov.: 30 AF XY: 0.0172 AC XY: 728 AN XY: 42316

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.00932

Gnomad4 ASJ AF: 0.0139

Gnomad4 EAS AF: 0.00469

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.00523

Gnomad4 NFE AF: 0.00402

Gnomad4 OTH AF: 0.0169

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;