Genetic Variant COP1:c.1142-11_1142-8delTTTT (chr1-176081294-GAAAA-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_022457.7(COP1):c.1142-11_1142-8delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,276,120 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 0.000011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

COP1
NM_022457.7 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 867 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COP1	NM_022457.7 link	c.1142-11_1142-8delTTTT		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 link	c.1142-11_1142-8delTTTT		splice_region_variant, intron_variant	Intron 10 of 19	1	NM_022457.7	ENSP00000356641.3		Q8NHY2-1

Frequencies

GnomAD3 genomes

AF:

0.0000110

AC:

AN:

90982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000223

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000732

AC:

867

AN:

1185130

Hom.:

AF XY:

0.000811

AC XY:

477

AN XY:

588422

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.00191

Gnomad4 ASJ exome

AF:

0.000908

Gnomad4 EAS exome

AF:

0.000546

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.000764

Gnomad4 NFE exome

AF:

0.000652

Gnomad4 OTH exome

AF:

0.000833

GnomAD4 genome

AF:

0.0000110

AC:

AN:

90990

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

42346

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000223

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over