Genetic Variant COP1:c.1142-14_1142-8delTTTTTTT (chr1-176081294-GAAAAAAA-G) – 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.1142-14_1142-8delTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,283,916 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 0.000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

COP1
NM_022457.7 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 6 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.1142-14_1142-8delTTTTTTT	splice_region intron	N/A	NP_071902.2
COP1	NM_001001740.4		c.1070-14_1070-8delTTTTTTT	splice_region intron	N/A	NP_001001740.1	Q8NHY2-2
COP1	NM_001286644.2		c.422-14_422-8delTTTTTTT	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.1142-14_1142-8delTTTTTTT	splice_region intron	N/A	ENSP00000356641.3	Q8NHY2-1
COP1	ENST00000308769.12	TSL:1	c.1070-14_1070-8delTTTTTTT	splice_region intron	N/A	ENSP00000310943.8	Q8NHY2-2
COP1	ENST00000367667.5	TSL:1	n.318-14_318-8delTTTTTTT	splice_region intron	N/A	ENSP00000356639.1	H0Y340

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

90990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000249

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:

0.00000838

AC:

AN:

1192918

Hom.:

AF XY:

0.00000675

AC XY:

AN XY:

592360

show subpopulations

African (AFR)

AF:

0.000230

AC:

AN:

26132

American (AMR)

AF:

0.00

AC:

AN:

25848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19960

East Asian (EAS)

AF:

0.00

AC:

AN:

34964

South Asian (SAS)

AF:

0.00

AC:

AN:

59702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

932362

Other (OTH)

AF:

0.0000605

AC:

AN:

49626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000659

AC:

AN:

90998

Hom.:

Cov.:

AF XY:

0.0000708

AC XY:

AN XY:

42354

show subpopulations

African (AFR)

AF:

0.000249

AC:

AN:

24114

American (AMR)

AF:

0.00

AC:

AN:

7952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2386

East Asian (EAS)

AF:

0.00

AC:

AN:

2984

South Asian (SAS)

AF:

0.00

AC:

AN:

3106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

44844

Other (OTH)

AF:

0.00

AC:

AN:

1188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.617

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.:

Bravo

AF:

0.0000416

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

Publications

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1-176081294-GAAAAAAAA-GA

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