dbSNP rs9462875: CUL9:c.3385-57A>G (chr6-43200379-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015089.4(CUL9):c.3385-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,613,092 control chromosomes in the GnomAD database, including 28,364 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 5512 hom., cov: 31)

Exomes 𝑓: 0.17 ( 22852 hom. )

Consequence

CUL9
NM_015089.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.598

Publications

16 publications found

Variant links:

Genes affected

CUL9 (HGNC:15982): (cullin 9) Predicted to enable several functions, including ATP binding activity; metal ion binding activity; and ubiquitin protein ligase binding activity. Involved in microtubule cytoskeleton organization; protein ubiquitination; and regulation of mitotic nuclear division. Located in cytosol. Part of cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

CUL9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015089.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL9	NM_015089.4	MANE Select	c.3385-57A>G		intron	N/A	NP_055904.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CUL9	ENST00000252050.9	TSL:5 MANE Select	c.3385-57A>G	intron	N/A	ENSP00000252050.4
CUL9	ENST00000372647.6	TSL:1	c.3385-57A>G	intron	N/A	ENSP00000361730.2
CUL9	ENST00000515773.5	TSL:2	n.3839-57A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35548

AN:

151744

Hom.:

5493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.197

GnomAD4 exome

AF:

0.169

AC:

246237

AN:

1461230

Hom.:

22852

Cov.:

AF XY:

0.167

AC XY:

121226

AN XY:

726910

show subpopulations

African (AFR)

AF:

0.456

AC:

15243

AN:

33452

American (AMR)

AF:

0.158

AC:

7083

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3314

AN:

26114

East Asian (EAS)

AF:

0.0287

AC:

1141

AN:

39698

South Asian (SAS)

AF:

0.143

AC:

12368

AN:

86220

European-Finnish (FIN)

AF:

0.107

AC:

5705

AN:

53412

Middle Eastern (MID)

AF:

0.171

AC:

986

AN:

5766

European-Non Finnish (NFE)

AF:

0.171

AC:

189872

AN:

1111496

Other (OTH)

AF:

0.174

AC:

10525

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11793

23586

35379

47172

58965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6802

13604

20406

27208

34010

<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:

0.235

AC:

35613

AN:

151862

Hom.:

5512

Cov.:

AF XY:

0.227

AC XY:

16848

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.446

AC:

18454

AN:

41360

American (AMR)

AF:

0.185

AC:

2827

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

467

AN:

3466

East Asian (EAS)

AF:

0.0217

AC:

112

AN:

5164

South Asian (SAS)

AF:

0.137

AC:

656

AN:

4800

European-Finnish (FIN)

AF:

0.104

AC:

1100

AN:

10544

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11297

AN:

67944

Other (OTH)

AF:

0.196

AC:

413

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1247

2494

3741

4988

6235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.178

Hom.:

4180

Bravo

AF:

0.251

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.70

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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