rs115556089

Variant names:

• chr6-43184766-C-T
• rs115556089
• NM_015089.4:c.456C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_015089.4(CUL9):​c.456C>T​(p.Tyr152Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,614,172 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: CUL9 NM_015089.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.22
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-43184766-C-T is Benign according to our data. Variant chr6-43184766-C-T is described in ClinVar as [Benign]. Clinvar id is 3042127.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL9	NM_015089.4	c.456C>T	p.Tyr152Tyr	synonymous_variant	Exon 2 of 41	ENST00000252050.9	NP_055904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL9	ENST00000252050.9	c.456C>T	p.Tyr152Tyr	synonymous_variant	Exon 2 of 41	5	NM_015089.4	ENSP00000252050.4
CUL9	ENST00000372647.6	c.456C>T	p.Tyr152Tyr	synonymous_variant	Exon 2 of 41	1		ENSP00000361730.2
CUL9	ENST00000451399.5	n.531C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2
CUL9	ENST00000515773.5	n.531C>T		non_coding_transcript_exon_variant	Exon 2 of 40	2

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 652 AN: 152232 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

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: 0.000279

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00130 AC: 326 AN: 251172 AF XY: 0.00113

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000510 AC: 746 AN: 1461822 Hom.: 3 Cov.: 31 AF XY: 0.000455 AC XY: 331 AN XY: 727222

African (AFR) AF: 0.0136 AC: 456 AN: 33480

American (AMR) AF: 0.00127 AC: 57 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1112010

Other (OTH) AF: 0.00154 AC: 93 AN: 60396

GnomAD4 genome AF: 0.00429 AC: 653 AN: 152350 Hom.: 1 Cov.: 32 AF XY: 0.00425 AC XY: 317 AN XY: 74510

African (AFR) AF: 0.0142 AC: 591 AN: 41578

American (AMR) AF: 0.00268 AC: 41 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68036

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00194 Hom.: 4

Bravo AF: 0.00461

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CUL9-related disorder Benign:1

Jan 02, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.84
DANN	Benign	0.83
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs115556089; hg19: chr6-43152504; COSMIC: COSV52726670; COSMIC: COSV52726670;