1-176081294-GAAAAAAAA-GAAA

Variant names:

• chr1-176081294-GAAAAA-G
• rs56720201
• NM_022457.7:c.1142-12_1142-8delTTTTT

Variant summary

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

The NM_022457.7(COP1):​c.1142-12_1142-8delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,282,694 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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: COP1 NM_022457.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• 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.1142-12_1142-8delTTTTT		splice_region intron	N/A	NP_071902.2
	COP1	NM_001001740.4		c.1070-12_1070-8delTTTTT		splice_region intron	N/A	NP_001001740.1	Q8NHY2-2
	COP1	NM_001286644.2		c.422-12_422-8delTTTTT		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.1142-12_1142-8delTTTTT		splice_region intron	N/A	ENSP00000356641.3	Q8NHY2-1
	COP1	ENST00000308769.12	TSL:1	c.1070-12_1070-8delTTTTT		splice_region intron	N/A	ENSP00000310943.8	Q8NHY2-2
	COP1	ENST00000367667.5	TSL:1	n.*318-12_*318-8delTTTTT		splice_region intron	N/A	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes AF: 0.0000220 AC: 2 AN: 90990 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000831

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000797 AC: 95 AN: 1191704 Hom.: 0 AF XY: 0.0000693 AC XY: 41 AN XY: 591754

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

African (AFR) AF: 0.0000766 AC: 2 AN: 26108

American (AMR) AF: 0.000349 AC: 9 AN: 25810

Ashkenazi Jewish (ASJ) AF: 0.0000501 AC: 1 AN: 19944

East Asian (EAS) AF: 0.0000573 AC: 2 AN: 34930

South Asian (SAS) AF: 0.000151 AC: 9 AN: 59614

European-Finnish (FIN) AF: 0.000202 AC: 8 AN: 39522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4754

European-Non Finnish (NFE) AF: 0.0000633 AC: 59 AN: 931446

Other (OTH) AF: 0.000101 AC: 5 AN: 49576

⚠️ 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: 0.0000220 AC: 2 AN: 90990 Hom.: 0 Cov.: 30 AF XY: 0.0000236 AC XY: 1 AN XY: 42324

African (AFR) AF: 0.0000831 AC: 2 AN: 24072

American (AMR) AF: 0.00 AC: 0 AN: 7944

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2996

South Asian (SAS) AF: 0.00 AC: 0 AN: 3124

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44850

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56720201; hg19: chr1-176050430;