Variant rs2273709 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015089.4(CUL9):c.6173A>C(p.His2058Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,613,862 control chromosomes in the GnomAD database, including 54,616 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 12157 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42459 hom. )

Consequence

CUL9
NM_015089.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.86

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3749712E-6).

BP6

Variant 6-43216394-A-C is Benign according to our data. Variant chr6-43216394-A-C is described in ClinVar as [Benign]. Clinvar id is 3058940.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL9	NM_015089.4 linkuse as main transcript	c.6173A>C	p.His2058Pro	missense_variant	31/41	ENST00000252050.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL9	ENST00000252050.9 linkuse as main transcript	c.6173A>C	p.His2058Pro	missense_variant	31/41	5	NM_015089.4	P2	Q8IWT3-1
	ENST00000500590.1 linkuse as main transcript	n.872-2485T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

52039

AN:

151972

Hom.:

12119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.252

AC:

62971

AN:

249452

Hom.:

10075

AF XY:

0.244

AC XY:

32924

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.405

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.226

AC:

330922

AN:

1461772

Hom.:

42459

Cov.:

AF XY:

0.225

AC XY:

163929

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.682

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.343

AC:

52138

AN:

152090

Hom.:

12157

Cov.:

AF XY:

0.339

AC XY:

25168

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.670

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.419

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.228

Hom.:

12255

Bravo

AF:

0.366

TwinsUK

AF:

0.206

AC:

764

ALSPAC

AF:

0.197

AC:

760

ESP6500AA

AF:

0.662

AC:

2916

ESP6500EA

AF:

0.210

AC:

1803

ExAC

AF:

0.261

AC:

31631

Asia WGS

AF:

0.331

AC:

1151

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.195

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CUL9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.031

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.074

T;T

MetaRNN

Benign

0.0000024

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.0

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0

B;B

Vest4

0.034

MPC

0.51

ClinPred

0.0052

GERP RS

5.7

Varity_R

0.097

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over