1-176081294-GAAAAAAAA-GAA

Variant names:

• chr1-176081294-GAAAAAA-G
• rs56720201
• NM_022457.7:c.1142-13_1142-8delTTTTTT

Variant summary

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

The NM_022457.7(COP1):​c.1142-13_1142-8delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000587 in 1,192,828 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: COP1 NM_022457.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• Publications: 0 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.1142-13_1142-8delTTTTTT		splice_region intron	N/A	NP_071902.2
	COP1	NM_001001740.4		c.1070-13_1070-8delTTTTTT		splice_region intron	N/A	NP_001001740.1	Q8NHY2-2
	COP1	NM_001286644.2		c.422-13_422-8delTTTTTT		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.1142-13_1142-8delTTTTTT		splice_region intron	N/A	ENSP00000356641.3	Q8NHY2-1
	COP1	ENST00000308769.12	TSL:1	c.1070-13_1070-8delTTTTTT		splice_region intron	N/A	ENSP00000310943.8	Q8NHY2-2
	COP1	ENST00000367667.5	TSL:1	n.*318-13_*318-8delTTTTTT		splice_region intron	N/A	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000587 AC: 7 AN: 1192828 Hom.: 0 AF XY: 0.00000506 AC XY: 3 AN XY: 592314

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

African (AFR) AF: 0.00 AC: 0 AN: 26130

American (AMR) AF: 0.00 AC: 0 AN: 25844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19958

East Asian (EAS) AF: 0.00 AC: 0 AN: 34964

South Asian (SAS) AF: 0.0000503 AC: 3 AN: 59696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39566

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

European-Non Finnish (NFE) AF: 0.00000429 AC: 4 AN: 932292

Other (OTH) AF: 0.00 AC: 0 AN: 49624

⚠️ 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 Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism

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;