6-43200379-A-G

Position:

• chr6-43200379-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CUL9	NM_015089.4	c.3385-57A>G		intron_variant		ENST00000252050.9	NP_055904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL9	ENST00000252050.9	c.3385-57A>G		intron_variant		5	NM_015089.4	ENSP00000252050	P2
CUL9	ENST00000372647.6	c.3385-57A>G		intron_variant		1		ENSP00000361730	A2
CUL9	ENST00000515773.5	n.3839-57A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35548 AN: 151744 Hom.: 5493 Cov.: 31

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.: 33 AF XY: 0.167 AC XY: 121226 AN XY: 726910

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.0287

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.235 AC: 35613 AN: 151862 Hom.: 5512 Cov.: 31 AF XY: 0.227 AC XY: 16848 AN XY: 74200

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0217

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.196

Alfa AF: 0.175 Hom.: 3374

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
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs9462875; hg19: chr6-43168117; COSMIC: COSV52728685; COSMIC: COSV52728685;