1-176081294-GAAA-G

Position:

• chr1-176081294-GAAA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_022457.7(COP1):​c.1142-10_1142-8delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,257,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0040 (0 hom.)
• Consequence: COP1 NM_022457.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

COP1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-176081294-GAAA-G is Benign according to our data. Variant chr1-176081294-GAAA-G is described in ClinVar as [Benign]. Clinvar id is 788692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 4665 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COP1	NM_022457.7	c.1142-10_1142-8delTTT		splice_region_variant, intron_variant		ENST00000367669.8	NP_071902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COP1	ENST00000367669.8	c.1142-10_1142-8delTTT		splice_region_variant, intron_variant		1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 3 AN: 90970 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000446

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00400 AC: 4665 AN: 1166606 Hom.: 0 AF XY: 0.00427 AC XY: 2472 AN XY: 579126

Gnomad4 AFR exome AF: 0.00411

Gnomad4 AMR exome AF: 0.00785

Gnomad4 ASJ exome AF: 0.00540

Gnomad4 EAS exome AF: 0.00348

Gnomad4 SAS exome AF: 0.00837

Gnomad4 FIN exome AF: 0.00512

Gnomad4 NFE exome AF: 0.00352

Gnomad4 OTH exome AF: 0.00473

GnomAD4 genome AF: 0.0000330 AC: 3 AN: 90970 Hom.: 0 Cov.: 30 AF XY: 0.0000236 AC XY: 1 AN XY: 42312

Gnomad4 AFR AF: 0.0000416

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000446

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 14, 2017

- -

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;