1-176081294-GAAAAAAAA-GAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_022457.7(COP1):​c.1142-9_1142-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,280,204 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0022 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000209 AC: 19 AN: 90982 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000831

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000419

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000334

Gnomad OTH AF: 0.000843

GnomAD4 exome AF: 0.00221 AC: 2626 AN: 1189222 Hom.: 0 Cov.: 0 AF XY: 0.00234 AC XY: 1385 AN XY: 590630

Gnomad4 AFR exome AF: 0.00234

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00236

Gnomad4 EAS exome AF: 0.00186

Gnomad4 SAS exome AF: 0.00422

Gnomad4 FIN exome AF: 0.00309

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.000209 AC: 19 AN: 90982 Hom.: 0 Cov.: 30 AF XY: 0.000236 AC XY: 10 AN XY: 42318

Gnomad4 AFR AF: 0.0000831

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000419

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000334

Gnomad4 OTH AF: 0.000843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;