Genetic Variant NM_015089.4: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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL9	NM_015089.4 link	c.3385-57A>G		intron_variant	Intron 14 of 40	ENST00000252050.9	NP_055904.1	Q8IWT3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUL9	ENST00000252050.9 link	c.3385-57A>G	intron_variant	Intron 14 of 40	5	NM_015089.4	ENSP00000252050.4	Q8IWT3-1
CUL9	ENST00000372647.6 link	c.3385-57A>G	intron_variant	Intron 14 of 40	1		ENSP00000361730.2	E9PEZ1
CUL9	ENST00000515773.5 link	n.3839-57A>G	intron_variant	Intron 13 of 39	2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over