1-176081294-GAAAAAAAA-GAAAAAA

Variant names:

• chr1-176081294-GAA-G
• rs56720201
• NM_022457.7:c.1142-9_1142-8delTT

Variant summary

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

The NM_022457.7(COP1):​c.1142-9_1142-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,204,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 (0 hom., cov: 30)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: COP1 NM_022457.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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 sas. gnomad4_exome allele frequency = 0.0273 (30418/1113814) while in subpopulation SAS AF= 0.0434 (2421/55768). AF 95% confidence interval is 0.042. There are 0 homozygotes in gnomad4_exome. There are 15676 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COP1	NM_022457.7	c.1142-9_1142-8delTT		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.1142-9_1142-8delTT		splice_region_variant, intron_variant	Intron 10 of 19	1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.000154 AC: 14 AN: 90950 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00157

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0273 AC: 30418 AN: 1113814 Hom.: 0 AF XY: 0.0283 AC XY: 15676 AN XY: 552972

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0348

Gnomad4 EAS exome AF: 0.0293

Gnomad4 SAS exome AF: 0.0434

Gnomad4 FIN exome AF: 0.0319

Gnomad4 NFE exome AF: 0.0252

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.000154 AC: 14 AN: 90958 Hom.: 0 Cov.: 30 AF XY: 0.000118 AC XY: 5 AN XY: 42334

Gnomad4 AFR AF: 0.0000415

Gnomad4 AMR AF: 0.000126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00157

Gnomad4 NFE AF: 0.000134

Gnomad4 OTH AF: 0.00

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;