1-176081294-GAAAAAAAA-GAAAA

Variant names:

• chr1-176081294-GAAAA-G
• rs56720201
• NM_022457.7:c.1142-11_1142-8delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022457.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COP1	NM_022457.7	MANE Select	c.1142-11_1142-8delTTTT		splice_region intron	N/A	NP_071902.2
	COP1	NM_001001740.4		c.1070-11_1070-8delTTTT		splice_region intron	N/A	NP_001001740.1	Q8NHY2-2
	COP1	NM_001286644.2		c.422-11_422-8delTTTT		splice_region intron	N/A	NP_001273573.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COP1	ENST00000367669.8	TSL:1 MANE Select	c.1142-11_1142-8delTTTT		splice_region intron	N/A	ENSP00000356641.3	Q8NHY2-1
	COP1	ENST00000308769.12	TSL:1	c.1070-11_1070-8delTTTT		splice_region intron	N/A	ENSP00000310943.8	Q8NHY2-2
	COP1	ENST00000367667.5	TSL:1	n.*318-11_*318-8delTTTT		splice_region intron	N/A	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes AF: 0.0000110 AC: 1 AN: 90982 Hom.: 0 Cov.: 30

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

GnomAD2 exomes AF: 0.00112 AC: 116 AN: 103470 AF XY: 0.00111

Gnomad AFR exome AF: 0.000834

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00211

Gnomad EAS exome AF: 0.000997

Gnomad FIN exome AF: 0.000338

Gnomad NFE exome AF: 0.000984

Gnomad OTH exome AF: 0.00299

GnomAD4 exome AF: 0.000732 AC: 867 AN: 1185130 Hom.: 0 AF XY: 0.000811 AC XY: 477 AN XY: 588422

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000539 AC: 14 AN: 25970

American (AMR) AF: 0.00191 AC: 49 AN: 25660

Ashkenazi Jewish (ASJ) AF: 0.000908 AC: 18 AN: 19832

East Asian (EAS) AF: 0.000546 AC: 19 AN: 34768

South Asian (SAS) AF: 0.00151 AC: 89 AN: 59130

European-Finnish (FIN) AF: 0.000764 AC: 30 AN: 39278

Middle Eastern (MID) AF: 0.000635 AC: 3 AN: 4722

European-Non Finnish (NFE) AF: 0.000652 AC: 604 AN: 926534

Other (OTH) AF: 0.000833 AC: 41 AN: 49236

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000110 AC: 1 AN: 90990 Hom.: 0 Cov.: 30 AF XY: 0.0000236 AC XY: 1 AN XY: 42346

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24112

American (AMR) AF: 0.00 AC: 0 AN: 7952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2386

East Asian (EAS) AF: 0.00 AC: 0 AN: 2984

South Asian (SAS) AF: 0.00 AC: 0 AN: 3106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 120

European-Non Finnish (NFE) AF: 0.0000223 AC: 1 AN: 44840

Other (OTH) AF: 0.00 AC: 0 AN: 1186

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs56720201; hg19: chr1-176050430;