Genetic Variant COP1:c.1142-9_1142-8dupTT (chr1-176081294-G-GAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_022457.7(COP1):c.1142-9_1142-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,280,204 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0022 ( 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 19 AD gene.

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.1142-9_1142-8dupTT	splice_region intron	N/A	NP_071902.2
COP1	NM_001001740.4		c.1070-9_1070-8dupTT	splice_region intron	N/A	NP_001001740.1	Q8NHY2-2
COP1	NM_001286644.2		c.422-9_422-8dupTT	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_1142-7insTT	splice_region intron	N/A	ENSP00000356641.3	Q8NHY2-1
COP1	ENST00000308769.12	TSL:1	c.1070-8_1070-7insTT	splice_region intron	N/A	ENSP00000310943.8	Q8NHY2-2
COP1	ENST00000367667.5	TSL:1	n.318-8_318-7insTT	splice_region intron	N/A	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes

AF:

0.000209

AC:

AN:

90982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000831

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000419

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000334

Gnomad OTH

AF:

0.000843

GnomAD2 exomes

AF:

0.00483

AC:

500

AN:

103470

AF XY:

0.00457

show subpopulations

Gnomad AFR exome

AF:

0.00528

Gnomad AMR exome

AF:

0.00412

Gnomad ASJ exome

AF:

0.00423

Gnomad EAS exome

AF:

0.00760

Gnomad FIN exome

AF:

0.00473

Gnomad NFE exome

AF:

0.00502

Gnomad OTH exome

AF:

0.00427

GnomAD4 exome

AF:

0.00221

AC:

2626

AN:

1189222

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

1385

AN XY:

590630

show subpopulations

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

African (AFR)

AF:

0.00234

AC:

AN:

26068

American (AMR)

AF:

0.00341

AC:

AN:

25790

Ashkenazi Jewish (ASJ)

AF:

0.00236

AC:

AN:

19922

East Asian (EAS)

AF:

0.00186

AC:

AN:

34928

South Asian (SAS)

AF:

0.00422

AC:

251

AN:

59532

European-Finnish (FIN)

AF:

0.00309

AC:

122

AN:

39460

Middle Eastern (MID)

AF:

0.000843

AC:

AN:

4744

European-Non Finnish (NFE)

AF:

0.00202

AC:

1874

AN:

929280

Other (OTH)

AF:

0.00230

AC:

114

AN:

49498

⚠️ 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: 0.301

Heterozygous variant carriers

194

388

581

775

969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

168

224

280

<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:

0.000209

AC:

AN:

90982

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

AN XY:

42318

show subpopulations

African (AFR)

AF:

0.0000831

AC:

AN:

24072

American (AMR)

AF:

0.00

AC:

AN:

7940

Ashkenazi Jewish (ASJ)

AF:

0.000419

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:

0.000334

AC:

AN:

44846

Other (OTH)

AF:

0.000843

AC:

AN:

1186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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-GAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over