Genetic Variant COP1:c.1142-10_1142-8dupTTT (chr1-176081294-G-GAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_022457.7(COP1):c.1142-10_1142-8dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,283,568 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: 𝑓 0.000011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

COP1
NM_022457.7 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.493

Publications

1 publications found

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 was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COP1	NM_022457.7	MANE Select	c.1142-10_1142-8dupTTT	splice_region intron	N/A	NP_071902.2
COP1	NM_001001740.4		c.1070-10_1070-8dupTTT	splice_region intron	N/A	NP_001001740.1	Q8NHY2-2
COP1	NM_001286644.2		c.422-10_422-8dupTTT	splice_region intron	N/A	NP_001273573.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COP1	ENST00000367669.8	TSL:1 MANE Select	c.1142-8_1142-7insTTT	splice_region intron	N/A	ENSP00000356641.3	Q8NHY2-1
COP1	ENST00000308769.12	TSL:1	c.1070-8_1070-7insTTT	splice_region intron	N/A	ENSP00000310943.8	Q8NHY2-2
COP1	ENST00000367667.5	TSL:1	n.318-8_318-7insTTT	splice_region intron	N/A	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes

AF:

0.0000110

AC:

AN:

90990

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:

0.000135

AC:

161

AN:

1192578

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

592186

show subpopulations

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

African (AFR)

AF:

0.0000765

AC:

AN:

26128

American (AMR)

AF:

0.000155

AC:

AN:

25842

Ashkenazi Jewish (ASJ)

AF:

0.000150

AC:

AN:

19958

East Asian (EAS)

AF:

0.000200

AC:

AN:

34966

South Asian (SAS)

AF:

0.000402

AC:

AN:

59672

European-Finnish (FIN)

AF:

0.000152

AC:

AN:

39558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

0.000120

AC:

112

AN:

932088

Other (OTH)

AF:

0.0000605

AC:

AN:

49612

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.302

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000110

AC:

AN:

90990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

42324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24072

American (AMR)

AF:

0.00

AC:

AN:

7944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2386

East Asian (EAS)

AF:

0.00

AC:

AN:

2996

South Asian (SAS)

AF:

0.00

AC:

AN:

3124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

128

European-Non Finnish (NFE)

AF:

0.0000223

AC:

AN:

44850

Other (OTH)

AF:

0.00

AC:

AN:

1186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.49

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-176081294-GAAAAAAAA-GAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over