chr1-176081294-G-A

Position:

• chr1-176081294-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_022457.7(COP1):​c.1142-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000822 in 1,192,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COP1 NM_022457.7 splice_region, intron
• Scores: Splicing: ADA: 0.00009299
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.563

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-176081294-G-A is Benign according to our data. Variant chr1-176081294-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 769544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome4 at 980 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COP1	NM_022457.7	c.1142-7C>T		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.1142-7C>T		splice_region_variant, intron_variant		1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 268 AN: 90594 Hom.: 0 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.00204

Gnomad AMI AF: 0.00429

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000842

Gnomad EAS AF: 0.00235

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000822 AC: 980 AN: 1192624 Hom.: 0 Cov.: 22 AF XY: 0.000932 AC XY: 552 AN XY: 592198

Gnomad4 AFR exome AF: 0.000727

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00100

Gnomad4 EAS exome AF: 0.00112

Gnomad4 SAS exome AF: 0.00230

Gnomad4 FIN exome AF: 0.00567

Gnomad4 NFE exome AF: 0.000508

Gnomad4 OTH exome AF: 0.000504

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00298 AC: 270 AN: 90602 Hom.: 0 Cov.: 25 AF XY: 0.00363 AC XY: 153 AN XY: 42182

Gnomad4 AFR AF: 0.00208

Gnomad4 AMR AF: 0.00354

Gnomad4 ASJ AF: 0.000842

Gnomad4 EAS AF: 0.00236

Gnomad4 SAS AF: 0.00226

Gnomad4 FIN AF: 0.0113

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000093
dbscSNV1_RF	Benign	0.0
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: rs879019998; hg19: chr1-176050430;