Variant 6-43184776-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015089.4(CUL9):c.466G>C(p.Gly156Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000731 in 1,614,098 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 11 hom. )

Consequence

CUL9
NM_015089.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.83

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007999241).

BP6

Variant 6-43184776-G-C is Benign according to our data. Variant chr6-43184776-G-C is described in ClinVar as [Benign]. Clinvar id is 3033339.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000655 (958/1461782) while in subpopulation AMR AF= 0.0199 (890/44724). AF 95% confidence interval is 0.0188. There are 11 homozygotes in gnomad4_exome. There are 406 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL9	NM_015089.4 link	c.466G>C	p.Gly156Arg	missense_variant	2/41	ENST00000252050.9	NP_055904.1	Q8IWT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CUL9	ENST00000252050.9 link	c.466G>C	p.Gly156Arg	missense_variant	2/41	5	NM_015089.4	ENSP00000252050.4	Q8IWT3-1
CUL9	ENST00000372647.6 link	c.466G>C	p.Gly156Arg	missense_variant	2/41	1		ENSP00000361730.2	E9PEZ1
CUL9	ENST00000451399.5 link	n.541G>C		non_coding_transcript_exon_variant	2/5	2
CUL9	ENST00000515773.5 link	n.541G>C		non_coding_transcript_exon_variant	2/40	2

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0127

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:

0.0000294

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00285

AC:

716

AN:

251048

Hom.:

AF XY:

0.00215

AC XY:

292

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.000655

AC:

958

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

406

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000993

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152316

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.00294

ExAC

AF:

0.00226

AC:

274

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CUL9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 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

0.20

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.62

D;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.17

Sift

Benign

0.030

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.037

B;B

Vest4

0.47

MutPred

0.54

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.29

MPC

0.41

ClinPred

0.10

GERP RS

2.0

Varity_R

0.15

gMVP

0.74

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

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